[{"language":[{"iso":"eng"}],"publication":"Cell Reports","date_updated":"2023-08-04T11:00:48Z","oa":1,"article_processing_charge":"No","issue":"10","title":"Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum","isi":1,"has_accepted_license":"1","intvolume":"        35","scopus_import":"1","pmid":1,"type":"journal_article","status":"public","author":[{"last_name":"Zhang","first_name":"Tingting","full_name":"Zhang, Tingting"},{"full_name":"Liu, Tengyuan","first_name":"Tengyuan","last_name":"Liu"},{"last_name":"Mora","full_name":"Mora, Natalia","first_name":"Natalia"},{"first_name":"Justine","full_name":"Guegan, Justine","last_name":"Guegan"},{"last_name":"Bertrand","full_name":"Bertrand, Mathilde","first_name":"Mathilde"},{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras","first_name":"Ximena","full_name":"Contreras, Ximena"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","first_name":"Andi H","full_name":"Hansen, Andi H"},{"full_name":"Streicher, Carmen","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher"},{"last_name":"Anderle","full_name":"Anderle, Marica","first_name":"Marica"},{"full_name":"Danda, Natasha","first_name":"Natasha","last_name":"Danda"},{"last_name":"Tiberi","full_name":"Tiberi, Luca","first_name":"Luca"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon"},{"full_name":"Hassan, Bassem A.","first_name":"Bassem A.","last_name":"Hassan"}],"month":"06","publication_identifier":{"eissn":[" 22111247"]},"oa_version":"Published Version","day":"08","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"creator":"cziletti","content_type":"application/pdf","file_size":8900385,"access_level":"open_access","relation":"main_file","success":1,"file_id":"9554","file_name":"2021_CellReports_Zhang.pdf","checksum":"7def3d42ebc8f5675efb6f38819e3e2e","date_created":"2021-06-15T14:01:35Z","date_updated":"2021-06-15T14:01:35Z"}],"file_date_updated":"2021-06-15T14:01:35Z","article_type":"original","_id":"8546","doi":"10.1016/j.celrep.2021.109208","acknowledgement":"This work was supported by the program “Investissements d’avenir” ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under the European Union’s Horizon 2020 research and innovation programme grant agreement no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.” Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant, and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility, iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2 mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies. B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .","year":"2021","citation":{"mla":"Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” <i>Cell Reports</i>, vol. 35, no. 10, 109208, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">10.1016/j.celrep.2021.109208</a>.","chicago":"Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">https://doi.org/10.1016/j.celrep.2021.109208</a>.","ista":"Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 35(10), 109208.","short":"T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen, C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell Reports 35 (2021).","ieee":"T. Zhang <i>et al.</i>, “Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum,” <i>Cell Reports</i>, vol. 35, no. 10. Elsevier, 2021.","ama":"Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. <i>Cell Reports</i>. 2021;35(10). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">10.1016/j.celrep.2021.109208</a>","apa":"Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan, B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109208\">https://doi.org/10.1016/j.celrep.2021.109208</a>"},"date_created":"2020-09-21T12:00:48Z","ec_funded":1,"article_number":"109208","related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.03.18.997205"}]},"project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration"}],"publisher":"Elsevier","date_published":"2021-06-08T00:00:00Z","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","department":[{"_id":"SiHi"}],"quality_controlled":"1","volume":35,"publication_status":"published","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"external_id":{"pmid":["34107249 "],"isi":["000659894300001"]},"abstract":[{"lang":"eng","text":"Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors."}]},{"ddc":["570"],"abstract":[{"text":"The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention.","lang":"eng"}],"external_id":{"isi":["000616763400002"],"pmid":["33431633"]},"publication_status":"published","date_published":"2021-02-03T00:00:00Z","publisher":"Society for Neuroscience","quality_controlled":"1","volume":41,"page":"813-822","department":[{"_id":"SiHi"}],"project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"ec_funded":1,"year":"2021","acknowledgement":"Work in the I.L.H.-O. laboratory was supported by European Research Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1, Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and 102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G. Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons Foundation SFARI Research Award, and National Institutes of Health/National Institute of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National Institutes of Health, National Institute of General Medical Sciences R01GM134363-01, and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the University of California San Diego School of Medicine.","keyword":["General Neuroscience"],"date_created":"2021-02-03T12:23:51Z","citation":{"apa":"Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N. V., Cardin, J. A., Voytek, B., &#38; Muotri, A. R. (2021). The logic of developing neocortical circuits in health and disease. <i>The Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">https://doi.org/10.1523/jneurosci.1655-20.2020</a>","mla":"Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits in Health and Disease.” <i>The Journal of Neuroscience</i>, vol. 41, no. 5, Society for Neuroscience, 2021, pp. 813–22, doi:<a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">10.1523/jneurosci.1655-20.2020</a>.","ista":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA, Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health and disease. The Journal of Neuroscience. 41(5), 813–822.","chicago":"Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri. “The Logic of Developing Neocortical Circuits in Health and Disease.” <i>The Journal of Neuroscience</i>. Society for Neuroscience, 2021. <a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">https://doi.org/10.1523/jneurosci.1655-20.2020</a>.","short":"I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A. Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.","ieee":"I. L. Hanganu-Opatz <i>et al.</i>, “The logic of developing neocortical circuits in health and disease,” <i>The Journal of Neuroscience</i>, vol. 41, no. 5. Society for Neuroscience, pp. 813–822, 2021.","ama":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical circuits in health and disease. <i>The Journal of Neuroscience</i>. 2021;41(5):813-822. doi:<a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">10.1523/jneurosci.1655-20.2020</a>"},"doi":"10.1523/jneurosci.1655-20.2020","_id":"9073","article_type":"original","file_date_updated":"2022-05-27T06:59:55Z","publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"month":"02","file":[{"file_id":"11414","file_name":"2021_JourNeuroscience_Hanganu.pdf","checksum":"578fd7ed1a0aef74bce61bea2d987b33","success":1,"date_updated":"2022-05-27T06:59:55Z","date_created":"2022-05-27T06:59:55Z","creator":"dernst","content_type":"application/pdf","access_level":"open_access","file_size":1031150,"relation":"main_file"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","day":"03","author":[{"full_name":"Hanganu-Opatz, Ileana L.","first_name":"Ileana L.","last_name":"Hanganu-Opatz"},{"last_name":"Butt","full_name":"Butt, Simon J. B.","first_name":"Simon J. B."},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon"},{"first_name":"Natalia V.","full_name":"De Marco García, Natalia V.","last_name":"De Marco García"},{"full_name":"Cardin, Jessica A.","first_name":"Jessica A.","last_name":"Cardin"},{"full_name":"Voytek, Bradley","first_name":"Bradley","last_name":"Voytek"},{"last_name":"Muotri","first_name":"Alysson R.","full_name":"Muotri, Alysson R."}],"type":"journal_article","status":"public","pmid":1,"isi":1,"intvolume":"        41","scopus_import":"1","has_accepted_license":"1","issue":"5","article_processing_charge":"No","oa":1,"date_updated":"2023-09-05T14:03:17Z","title":"The logic of developing neocortical circuits in health and disease","publication":"The Journal of Neuroscience","language":[{"iso":"eng"}]},{"ec_funded":1,"date_created":"2021-02-04T07:23:23Z","citation":{"ieee":"D. J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous identification of brain cell type and lineage via single cell RNA sequencing,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","ama":"Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.12.31.425016\">10.1101/2020.12.31.425016</a>","short":"D.J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, BioRxiv (n.d.).","mla":"Anderson, Donovan J., et al. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.12.31.425016\">10.1101/2020.12.31.425016</a>.","ista":"Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. bioRxiv, <a href=\"https://doi.org/10.1101/2020.12.31.425016\">10.1101/2020.12.31.425016</a>.","chicago":"Anderson, Donovan J., Florian Pauler, Aaron McKenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Identification of Brain Cell Type and Lineage via Single Cell RNA Sequencing.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.12.31.425016\">https://doi.org/10.1101/2020.12.31.425016</a>.","apa":"Anderson, D. J., Pauler, F., McKenna, A., Shendure, J., Hippenmeyer, S., &#38; Horwitz, M. S. (n.d.). Simultaneous identification of brain cell type and lineage via single cell RNA sequencing. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.12.31.425016\">https://doi.org/10.1101/2020.12.31.425016</a>"},"title":"Simultaneous identification of brain cell type and lineage via single cell RNA sequencing","date_updated":"2021-02-04T07:29:53Z","acknowledgement":"We thank Bill Bolosky, Microsoft Research, for earlier work showing proof of concept in TCGA\r\nbulk RNA-seq data. Supported by the Paul G. Allen Frontiers Group (University of Washington);\r\nNIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant\r\n(C13-002) to SH, and the European Research Council (ERC) under the European Union’s\r\nHorizon 2020 research and innovation program 725780 LinPro to SH.","oa":1,"year":"2021","article_processing_charge":"No","doi":"10.1101/2020.12.31.425016","publication":"bioRxiv","language":[{"iso":"eng"}],"_id":"9082","oa_version":"Preprint","day":"01","main_file_link":[{"url":"https://doi.org/10.1101/2020.12.31.425016","open_access":"1"}],"abstract":[{"text":"Acquired mutations are sufficiently frequent such that the genome of a single cell offers a record of its history of cell divisions. Among more common somatic genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic expression for constitutionally heterozygous single nucleotide variants (SNVs) located among contiguous genes. We identified runs of monoallelic expression, consistent with LOH, uniquely distributed throughout the genome in single cell brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains. We then phylogenetically reconstructed single cell lineages and simultaneously identified cell types by corresponding gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. Compared to engineered recording systems, LOH events accumulate throughout the genome and across the lifetime of an organism, affording tremendous capacity for encoding lineage information and increasing resolution for later cell divisions. This approach can conceivably be computationally incorporated into scRNA-seq analysis and may be useful for organisms where genetic engineering is prohibitive, such as humans.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","publication_status":"submitted","author":[{"last_name":"Anderson","full_name":"Anderson, Donovan J.","first_name":"Donovan J."},{"last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian"},{"last_name":"McKenna","first_name":"Aaron","full_name":"McKenna, Aaron"},{"first_name":"Jay","full_name":"Shendure, Jay","last_name":"Shendure"},{"orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon"},{"full_name":"Horwitz, Marshall S.","first_name":"Marshall S.","last_name":"Horwitz"}],"department":[{"_id":"SiHi"}],"publisher":"Cold Spring Harbor Laboratory","date_published":"2021-01-01T00:00:00Z","status":"public","type":"preprint","project":[{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}]},{"ec_funded":1,"article_number":"104986","acknowledgement":"We thank Melissa Stouffer for critically reading the manuscript. This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung n[f + b] life science call grant (C13-002) to S.H. and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","year":"2021","date_created":"2021-02-23T12:31:43Z","citation":{"apa":"Pauler, F., Hudson, Q., Laukoter, S., &#38; Hippenmeyer, S. (2021). Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. <i>Neurochemistry International</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">https://doi.org/10.1016/j.neuint.2021.104986</a>","chicago":"Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer. “Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell Level in Brain and Beyond.” <i>Neurochemistry International</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">https://doi.org/10.1016/j.neuint.2021.104986</a>.","ista":"Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry International. 145(5), 104986.","mla":"Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell Level in Brain and Beyond.” <i>Neurochemistry International</i>, vol. 145, no. 5, 104986, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">10.1016/j.neuint.2021.104986</a>.","ama":"Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. <i>Neurochemistry International</i>. 2021;145(5). doi:<a href=\"https://doi.org/10.1016/j.neuint.2021.104986\">10.1016/j.neuint.2021.104986</a>","ieee":"F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond,” <i>Neurochemistry International</i>, vol. 145, no. 5. Elsevier, 2021.","short":"F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International 145 (2021)."},"keyword":["Cell Biology","Cellular and Molecular Neuroscience"],"doi":"10.1016/j.neuint.2021.104986","file_date_updated":"2021-08-11T12:30:38Z","article_type":"original","_id":"9188","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"external_id":{"isi":["000635575000005"],"pmid":["33600873"]},"abstract":[{"text":"Genomic imprinting is an epigenetic mechanism that results in parental allele-specific expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental regulators and play pivotal roles in many biological processes such as nutrient transfer from the mother to offspring and neuronal development. Imprinted genes are also involved in human disease, including neurodevelopmental disorders, and often occur in clusters that are regulated by a common imprint control region (ICR). In extra-embryonic tissues ICRs can act over large distances, with the largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical imprinted expression that shows near exclusive maternal or paternal expression, widespread biased imprinted expression has been identified mainly in brain. In this review we discuss recent developments mapping cell type specific imprinted expression in extra-embryonic tissues and neocortex in the mouse. We highlight the advantages of using an inducible uniparental chromosome disomy (UPD) system to generate cells carrying either two maternal or two paternal copies of a specific chromosome to analyze the functional consequences of genomic imprinting. Mosaic Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant induction of UPD sparsely in specific cell types, and thus to over-express or suppress all imprinted genes on that chromosome. To illustrate the utility of this technique, we explain how MADM-induced UPD revealed new insights about the function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs led to identification of highly cell type specific phenotypes related to perturbed imprinted expression in the mouse neocortex. Finally, we give an outlook on how MADM could be used to probe cell type specific imprinted expression in other tissues in mouse, particularly in extra-embryonic tissues.","lang":"eng"}],"publication_status":"published","publisher":"Elsevier","date_published":"2021-05-01T00:00:00Z","department":[{"_id":"SiHi"}],"volume":145,"quality_controlled":"1","project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002"}],"isi":1,"has_accepted_license":"1","intvolume":"       145","scopus_import":"1","date_updated":"2023-08-07T13:48:26Z","oa":1,"article_processing_charge":"Yes (via OA deal)","issue":"5","title":"Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond","publication":"Neurochemistry International","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0197-0186"]},"month":"05","day":"01","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"success":1,"file_id":"9883","file_name":"2021_NCI_Pauler.pdf","checksum":"c6d7a40089cd29e289f9b22e75768304","date_created":"2021-08-11T12:30:38Z","date_updated":"2021-08-11T12:30:38Z","creator":"kschuh","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_size":7083499}],"author":[{"last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian"},{"last_name":"Hudson","full_name":"Hudson, Quanah","first_name":"Quanah"},{"last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","full_name":"Laukoter, Susanne"},{"orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon"}],"pmid":1,"status":"public","type":"journal_article"},{"type":"technical_report","status":"public","alternative_title":["Nature Neuroscience"],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"23","main_file_link":[{"url":"https://doi.org/10.1038/s41593-021-00906-5","open_access":"1"}],"oa_version":"Published Version","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"month":"08","author":[{"full_name":"Samarasinghe, Ranmal A.","first_name":"Ranmal A.","last_name":"Samarasinghe"},{"first_name":"Osvaldo","full_name":"Miranda, Osvaldo","orcid":"0000-0001-6618-6889","last_name":"Miranda","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425"},{"last_name":"Buth","full_name":"Buth, Jessie E.","first_name":"Jessie E."},{"last_name":"Mitchell","full_name":"Mitchell, Simon","first_name":"Simon"},{"first_name":"Isabella","full_name":"Ferando, Isabella","last_name":"Ferando"},{"last_name":"Watanabe","full_name":"Watanabe, Momoko","first_name":"Momoko"},{"last_name":"Kurdian","first_name":"Arinnae","full_name":"Kurdian, Arinnae"},{"last_name":"Golshani","full_name":"Golshani, Peyman","first_name":"Peyman"},{"first_name":"Kathrin","full_name":"Plath, Kathrin","last_name":"Plath"},{"first_name":"William E.","full_name":"Lowry, William E.","last_name":"Lowry"},{"last_name":"Parent","first_name":"Jack M.","full_name":"Parent, Jack M."},{"full_name":"Mody, Istvan","first_name":"Istvan","last_name":"Mody"},{"last_name":"Novitch","full_name":"Novitch, Bennett G.","first_name":"Bennett G."}],"language":[{"iso":"eng"}],"intvolume":"        24","isi":1,"title":"Identification of neural oscillations and epileptiform changes in human brain organoids","article_processing_charge":"Yes","oa":1,"date_updated":"2023-08-04T10:49:44Z","volume":24,"page":"32","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"date_published":"2021-08-23T00:00:00Z","publisher":"Springer Nature","abstract":[{"lang":"eng","text":"Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery."}],"external_id":{"pmid":["34426698 "],"isi":["000687516300001"]},"publication_status":"published","doi":"10.1038/s41593-021-00906-5","_id":"6995","date_created":"2019-11-10T11:23:58Z","citation":{"apa":"Samarasinghe, R. A., Miranda, O., Buth, J. E., Mitchell, S., Ferando, I., Watanabe, M., … Novitch, B. G. (2021). <i>Identification of neural oscillations and epileptiform changes in human brain organoids</i> (Vol. 24). Springer Nature. <a href=\"https://doi.org/10.1038/s41593-021-00906-5\">https://doi.org/10.1038/s41593-021-00906-5</a>","chicago":"Samarasinghe, Ranmal A., Osvaldo Miranda, Jessie E. Buth, Simon Mitchell, Isabella Ferando, Momoko Watanabe, Arinnae Kurdian, et al. <i>Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids</i>. Vol. 24. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41593-021-00906-5\">https://doi.org/10.1038/s41593-021-00906-5</a>.","mla":"Samarasinghe, Ranmal A., et al. <i>Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids</i>. Vol. 24, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41593-021-00906-5\">10.1038/s41593-021-00906-5</a>.","ista":"Samarasinghe RA, Miranda O, Buth JE, Mitchell S, Ferando I, Watanabe M, Kurdian A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2021. Identification of neural oscillations and epileptiform changes in human brain organoids, Springer Nature, 32p.","short":"R.A. Samarasinghe, O. Miranda, J.E. Buth, S. Mitchell, I. Ferando, M. Watanabe, A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch, Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids, Springer Nature, 2021.","ama":"Samarasinghe RA, Miranda O, Buth JE, et al. <i>Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids</i>. Vol 24. Springer Nature; 2021. doi:<a href=\"https://doi.org/10.1038/s41593-021-00906-5\">10.1038/s41593-021-00906-5</a>","ieee":"R. A. Samarasinghe <i>et al.</i>, <i>Identification of neural oscillations and epileptiform changes in human brain organoids</i>, vol. 24. Springer Nature, 2021."},"year":"2021","acknowledgement":"We thank S. Butler, T. Carmichael and members of the laboratory of B.G.N. for helpful discussions and comments on the manuscript; N. Vishlaghi and F. Turcios-Hernandez for technical assistance, and J. Lee, S.-K. Lee, H. Shinagawa and K. Yoshikawa for valuable reagents. We also thank the UCLA Eli and Edythe Broad Stem Cell Research Center (BSCRC) and Intellectual and Developmental Disabilities Research Center microscopy cores for access to imaging facilities. This work was supported by grants from the California Institute for Regenerative Medicine (CIRM) (DISC1-08819 to B.G.N.), the National Institute of Health (R01NS089817, R01DA051897 and P50HD103557 to B.G.N.; K08NS119747 to R.A.S.; K99HD096105 to M.W.; R01MH123922, R01MH121521 and P50HD103557 to M.J.G.; R01GM099134 to K.P.; R01NS103788 to W.E.L.; R01NS088571 to J.M.P.; R01NS030549 and R01AG050474 to I.M.), and research awards from the UCLA Jonsson Comprehensive Cancer Center and BSCRC Ablon Scholars Program (to B.G.N.), the BSCRC Innovation Program (to B.G.N., K.P. and W.E.L.), the UCLA BSCRC Steffy Brain Aging Research Fund (to B.G.N. and W.E.L.) and the UCLA Clinical and Translational Science Institute (to B.G.N.), Paul Allen Family Foundation Frontiers Group (to K.P. and W.E.L.), the March of Dimes Foundation (to W.E.L.) and the Simons Foundation Autism Research Initiative Bridge to Independence Program (to R.A.S. and M.J.G.). R.A.S. was also supported by the UCLA/NINDS Translational Neuroscience Training Grant (R25NS065723), a Research and Training Fellowship from the American Epilepsy Society, a Taking Flight Award from CURE Epilepsy and a Clinician Scientist training award from the UCLA BSCRC. J.E.B. was supported by the UCLA BSCRC Rose Hills Foundation Graduate Scholarship Training Program. M.W. was supported by postdoctoral training awards provided by the UCLA BSCRC and the Uehara Memorial Foundation. O.A.M. and A.K. were supported in part by the UCLA-California State University Northridge CIRM-Bridges training program (EDUC2-08411). We also acknowledge the support of the IDDRC Cells, Circuits and Systems Analysis, Microscopy and Genetics and Genomics Cores of the Semel Institute of Neuroscience at UCLA, which are supported by the NICHD (U54HD087101 and P50HD10355701). We lastly acknowledge support from a Quantitative and Computational Biosciences Collaboratory Postdoctoral Fellowship to S.M. and the Quantitative and Computational Biosciences Collaboratory community, directed by M. Pellegrini."},{"publication_status":"published","ddc":["573"],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).","lang":"eng"}],"project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"grant_number":"T0101031","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression"}],"publisher":"Cell Press","date_published":"2021-11-10T00:00:00Z","department":[{"_id":"SiHi"}],"quality_controlled":"1","volume":2,"acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical Facilities (PCF). We particularly thank Mohammad Goudarzi for assistance with photography of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","year":"2021","citation":{"ista":"Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.","mla":"Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate Genes in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>, vol. 2, no. 4, 100939, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">10.1016/j.xpro.2021.100939</a>.","chicago":"Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate Genes in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">https://doi.org/10.1016/j.xpro.2021.100939</a>.","ieee":"N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers,” <i>STAR Protocols</i>, vol. 2, no. 4. Cell Press, 2021.","ama":"Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. 2021;2(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">10.1016/j.xpro.2021.100939</a>","short":"N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).","apa":"Amberg, N., &#38; Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. <i>STAR Protocols</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.xpro.2021.100939\">https://doi.org/10.1016/j.xpro.2021.100939</a>"},"date_created":"2021-11-21T23:01:28Z","ec_funded":1,"article_number":"100939","file_date_updated":"2021-11-22T08:23:58Z","_id":"10321","article_type":"original","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"doi":"10.1016/j.xpro.2021.100939","author":[{"orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole","full_name":"Amberg, Nicole"},{"orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon"}],"month":"11","publication_identifier":{"eissn":["2666-1667"]},"oa_version":"Published Version","day":"10","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_size":7309464,"creator":"cchlebak","date_updated":"2021-11-22T08:23:58Z","date_created":"2021-11-22T08:23:58Z","file_id":"10329","file_name":"2021_STARProtocols_Amberg.pdf","checksum":"9e3f6d06bf583e7a8b6a9e9a60500a28","success":1}],"status":"public","type":"journal_article","oa":1,"date_updated":"2023-11-16T13:08:03Z","issue":"4","article_processing_charge":"Yes","title":"Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers","intvolume":"         2","scopus_import":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"publication":"STAR Protocols"},{"publication":"Molecular Therapy - Methods and Clinical Development","language":[{"iso":"eng"}],"isi":1,"has_accepted_license":"1","intvolume":"        23","scopus_import":"1","article_processing_charge":"Yes","oa":1,"date_updated":"2023-11-16T13:12:03Z","title":"Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment","type":"journal_article","status":"public","publication_identifier":{"eissn":["2329-0501"]},"month":"12","file":[{"creator":"cchlebak","relation":"main_file","access_level":"open_access","file_size":4794147,"content_type":"application/pdf","file_id":"10657","checksum":"77dc540e8011c5475031bdf6ccef20a6","file_name":"2021_MolTherMethodsClinDev_Maes.pdf","success":1,"date_updated":"2022-01-24T07:43:09Z","date_created":"2022-01-24T07:43:09Z"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","day":"10","oa_version":"Published Version","author":[{"orcid":"0000-0001-9642-1085","id":"3838F452-F248-11E8-B48F-1D18A9856A87","last_name":"Maes","full_name":"Maes, Margaret E","first_name":"Margaret E"},{"last_name":"Wögenstein","full_name":"Wögenstein, Gabriele M.","first_name":"Gabriele M."},{"full_name":"Colombo, Gloria","first_name":"Gloria","orcid":"0000-0001-9434-8902","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","last_name":"Colombo"},{"last_name":"Casado Polanco","id":"15240fc1-dbcd-11ea-9d1d-ac5a786425fd","orcid":"0000-0001-8293-4568","full_name":"Casado Polanco, Raquel","first_name":"Raquel"},{"full_name":"Siegert, Sandra","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert"}],"doi":"10.1016/j.omtm.2021.09.006","_id":"10655","article_type":"original","file_date_updated":"2022-01-24T07:43:09Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ec_funded":1,"year":"2021","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 715571). The research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility, the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger and Michael Schunn for their animal colony management and support. We would also like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally, we would like to thank the Siegert team members for discussion about the manuscript.","date_created":"2022-01-23T23:01:28Z","citation":{"apa":"Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., &#38; Siegert, S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. <i>Molecular Therapy - Methods and Clinical Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">https://doi.org/10.1016/j.omtm.2021.09.006</a>","mla":"Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” <i>Molecular Therapy - Methods and Clinical Development</i>, vol. 23, Elsevier, 2021, pp. 210–24, doi:<a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">10.1016/j.omtm.2021.09.006</a>.","chicago":"Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” <i>Molecular Therapy - Methods and Clinical Development</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">https://doi.org/10.1016/j.omtm.2021.09.006</a>.","ista":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 23, 210–224.","ieee":"M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert, “Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment,” <i>Molecular Therapy - Methods and Clinical Development</i>, vol. 23. Elsevier, pp. 210–224, 2021.","ama":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. <i>Molecular Therapy - Methods and Clinical Development</i>. 2021;23:210-224. doi:<a href=\"https://doi.org/10.1016/j.omtm.2021.09.006\">10.1016/j.omtm.2021.09.006</a>","short":"M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular Therapy - Methods and Clinical Development 23 (2021) 210–224."},"date_published":"2021-12-10T00:00:00Z","publisher":"Elsevier","quality_controlled":"1","volume":23,"department":[{"_id":"SaSi"},{"_id":"SiHi"}],"page":"210-224","project":[{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571","name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"abstract":[{"lang":"eng","text":"Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.\r\n"}],"external_id":{"isi":["000748748500019"]},"publication_status":"published"},{"publication_status":"published","abstract":[{"text":"In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.","lang":"eng"}],"external_id":{"isi":["000667248600005"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"volume":12,"quality_controlled":"1","department":[{"_id":"SiHi"}],"date_published":"2021-07-12T00:00:00Z","publisher":"Springer Nature","citation":{"ama":"Santini L, Halbritter F, Titz-Teixeira F, et al. Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23510-4\">10.1038/s41467-021-23510-4</a>","ieee":"L. Santini <i>et al.</i>, “Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","short":"L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, X. Ma, J. Ramesmayer, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik, C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, Nature Communications 12 (2021).","mla":"Santini, Laura, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly Associated with H3K27me3.” <i>Nature Communications</i>, vol. 12, no. 1, 3804, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23510-4\">10.1038/s41467-021-23510-4</a>.","chicago":"Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Xiaoyan Ma, Julia Ramesmayer, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly Associated with H3K27me3.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23510-4\">https://doi.org/10.1038/s41467-021-23510-4</a>.","ista":"Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ma X, Ramesmayer J, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer A, Perry ACF, Leeb M. 2021. Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. Nature Communications. 12(1), 3804.","apa":"Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ma, X., … Leeb, M. (2021). Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23510-4\">https://doi.org/10.1038/s41467-021-23510-4</a>"},"date_created":"2021-06-27T22:01:46Z","year":"2021","acknowledgement":"The authors thank Robert Feil and Anton Wutz for helpful discussions and comments, Samuel Collombet and Peter Fraser for sharing embryo TAD coordinates, and Andy Riddel at the Cambridge Stem Cell Institute and Thomas Sauer at the Max Perutz Laboratories FACS facility for flow-sorting. We thank the team of the Biomedical Sequencing Facility at the CeMM and the Vienna Biocenter Core Facilities (VBCF) for support with next-generation sequencing. We are grateful to animal care teams at the University of Bath and MRC Harwell. A.C.F.P. acknowledges support from the UK Medical Research Council (MR/N000080/1 and MR/N020294/1) and Biotechnology and Biological Sciences Research Council (BB/P009506/1). L.S. is part of the FWF doctoral programme SMICH and supported by an Austrian Academy of Sciences DOC Fellowship. M.L. is funded by a Vienna Research Group for Young Investigators grant (VRG14-006) by the Vienna Science and Technology Fund (WWTF) and by the Austrian Science Fund FWF (I3786 and P31334).","article_number":"3804","_id":"9601","article_type":"original","file_date_updated":"2021-06-28T08:04:22Z","doi":"10.1038/s41467-021-23510-4","author":[{"full_name":"Santini, Laura","first_name":"Laura","last_name":"Santini"},{"full_name":"Halbritter, Florian","first_name":"Florian","last_name":"Halbritter"},{"last_name":"Titz-Teixeira","full_name":"Titz-Teixeira, Fabian","first_name":"Fabian"},{"last_name":"Suzuki","full_name":"Suzuki, Toru","first_name":"Toru"},{"full_name":"Asami, Maki","first_name":"Maki","last_name":"Asami"},{"first_name":"Xiaoyan","full_name":"Ma, Xiaoyan","last_name":"Ma"},{"first_name":"Julia","full_name":"Ramesmayer, Julia","last_name":"Ramesmayer"},{"first_name":"Andreas","full_name":"Lackner, Andreas","last_name":"Lackner"},{"last_name":"Warr","full_name":"Warr, Nick","first_name":"Nick"},{"full_name":"Pauler, Florian","first_name":"Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Laue","first_name":"Ernest","full_name":"Laue, Ernest"},{"first_name":"Matthias","full_name":"Farlik, Matthias","last_name":"Farlik"},{"last_name":"Bock","full_name":"Bock, Christoph","first_name":"Christoph"},{"last_name":"Beyer","first_name":"Andreas","full_name":"Beyer, Andreas"},{"last_name":"Perry","first_name":"Anthony C.F.","full_name":"Perry, Anthony C.F."},{"full_name":"Leeb, Martin","first_name":"Martin","last_name":"Leeb"}],"file":[{"checksum":"75dd89d09945185b2d14b2434a0bcb50","file_name":"2021_NatureCommunications_Santini.pdf","file_id":"9608","success":1,"date_updated":"2021-06-28T08:04:22Z","date_created":"2021-06-28T08:04:22Z","creator":"asandaue","content_type":"application/pdf","file_size":2156554,"relation":"main_file","access_level":"open_access"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","day":"12","month":"07","publication_identifier":{"eissn":["20411723"]},"type":"journal_article","status":"public","title":"Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3","issue":"1","article_processing_charge":"No","oa":1,"date_updated":"2023-08-10T13:53:23Z","has_accepted_license":"1","scopus_import":"1","intvolume":"        12","isi":1,"language":[{"iso":"eng"}],"publication":"Nature Communications"},{"author":[{"first_name":"Ximena","full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","orcid":"0000-0002-3183-8207","first_name":"Nicole","full_name":"Amberg, Nicole"},{"last_name":"Davaatseren","id":"70ADC922-B424-11E9-99E3-BA18E6697425","first_name":"Amarbayasgalan","full_name":"Davaatseren, Amarbayasgalan"},{"full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen"},{"last_name":"Sonntag","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","first_name":"Johanna","full_name":"Sonntag, Johanna"},{"first_name":"Lill","full_name":"Andersen, Lill","last_name":"Andersen"},{"first_name":"Tina","full_name":"Bernthaler, Tina","last_name":"Bernthaler"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","full_name":"Streicher, Carmen","first_name":"Carmen"},{"full_name":"Heger, Anna-Magdalena","first_name":"Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","last_name":"Heger"},{"full_name":"Johnson, Randy L.","first_name":"Randy L.","last_name":"Johnson"},{"first_name":"Lindsay A.","full_name":"Schwarz, Lindsay A.","last_name":"Schwarz"},{"last_name":"Luo","first_name":"Liqun","full_name":"Luo, Liqun"},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"}],"month":"06","publication_identifier":{"eissn":["22111247"]},"oa_version":"Published Version","day":"22","file":[{"creator":"asandaue","file_size":7653149,"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2021_CellReports_Contreras.pdf","file_id":"9613","checksum":"d49520fdcbbb5c2f883bddb67cee5d77","success":1,"date_updated":"2021-06-28T14:06:24Z","date_created":"2021-06-28T14:06:24Z"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","type":"journal_article","date_updated":"2023-08-10T13:55:00Z","oa":1,"issue":"12","article_processing_charge":"No","title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","isi":1,"scopus_import":"1","has_accepted_license":"1","intvolume":"        35","language":[{"iso":"eng"}],"publication":"Cell Reports","publication_status":"published","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"external_id":{"isi":["000664463600016"]},"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division."}],"project":[{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","call_identifier":"FP7","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"publisher":"Cell Press","date_published":"2021-06-22T00:00:00Z","department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"quality_controlled":"1","volume":35,"acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.","year":"2021","citation":{"apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>","chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">https://doi.org/10.1016/j.celrep.2021.109274</a>.","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>.","ieee":"X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021.","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109274\">10.1016/j.celrep.2021.109274</a>","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021)."},"date_created":"2021-06-27T22:01:48Z","ec_funded":1,"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/"}]},"article_number":"109274","file_date_updated":"2021-06-28T14:06:24Z","_id":"9603","article_type":"original","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"doi":"10.1016/j.celrep.2021.109274"},{"publication":"Neuron","language":[{"iso":"eng"}],"isi":1,"scopus_import":"1","intvolume":"       109","oa":1,"date_updated":"2023-09-27T07:46:09Z","issue":"15","article_processing_charge":"No","title":"HepaCAM controls astrocyte self-organization and coupling","pmid":1,"status":"public","type":"journal_article","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"month":"08","day":"04","oa_version":"Published Version","main_file_link":[{"url":"https://doi.org/10.1016/j.neuron.2021.05.025","open_access":"1"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Baldwin, Katherine T.","first_name":"Katherine T.","last_name":"Baldwin"},{"last_name":"Tan","first_name":"Christabel X.","full_name":"Tan, Christabel X."},{"first_name":"Samuel T.","full_name":"Strader, Samuel T.","last_name":"Strader"},{"last_name":"Jiang","first_name":"Changyu","full_name":"Jiang, Changyu"},{"full_name":"Savage, Justin T.","first_name":"Justin T.","last_name":"Savage"},{"last_name":"Elorza-Vidal","first_name":"Xabier","full_name":"Elorza-Vidal, Xabier"},{"first_name":"Ximena","full_name":"Contreras, Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","first_name":"Simon"},{"last_name":"Estévez","full_name":"Estévez, Raúl","first_name":"Raúl"},{"first_name":"Ru-Rong","full_name":"Ji, Ru-Rong","last_name":"Ji"},{"full_name":"Eroglu, Cagla","first_name":"Cagla","last_name":"Eroglu"}],"doi":"10.1016/j.neuron.2021.05.025","article_type":"original","_id":"9793","ec_funded":1,"acknowledgement":"This work was supported by the National Institutes of Health (R01 DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer lab was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte for assistance with proteomic experiments, and Dr. D. Silver for critical review of the manuscript. Cartoon elements of figure panels were created using BioRender.com.","year":"2021","citation":{"chicago":"Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang, Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls Astrocyte Self-Organization and Coupling.” <i>Neuron</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">https://doi.org/10.1016/j.neuron.2021.05.025</a>.","ista":"Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.","mla":"Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization and Coupling.” <i>Neuron</i>, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10, doi:<a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">10.1016/j.neuron.2021.05.025</a>.","short":"K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal, X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron 109 (2021) 2427–2442.e10.","ieee":"K. T. Baldwin <i>et al.</i>, “HepaCAM controls astrocyte self-organization and coupling,” <i>Neuron</i>, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.","ama":"Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization and coupling. <i>Neuron</i>. 2021;109(15):2427-2442.e10. doi:<a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">10.1016/j.neuron.2021.05.025</a>","apa":"Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal, X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2021.05.025\">https://doi.org/10.1016/j.neuron.2021.05.025</a>"},"date_created":"2021-08-06T09:08:25Z","publisher":"Elsevier","date_published":"2021-08-04T00:00:00Z","department":[{"_id":"SiHi"}],"page":"2427-2442.e10","quality_controlled":"1","volume":109,"project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020"}],"external_id":{"pmid":["34171291"],"isi":["000692851900010"]},"abstract":[{"lang":"eng","text":"Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate developmental processes among one another to parse out the synaptic neuropil and form non-overlapping territories is unknown. Here we identify a molecular mechanism regulating astrocyte-astrocyte interactions during development to coordinate astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked, astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for territory and morphological complexity in the developing mouse cortex. Furthermore, conditional deletion of Hepacam from developing astrocytes significantly impairs gap junction coupling between astrocytes and disrupts the balance between synaptic excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts in humans. Therefore, our findings suggest that disruption of astrocyte self-organization mechanisms could be an underlying cause of neural pathology."}],"publication_status":"published"},{"_id":"9906","article_type":"original","file_date_updated":"2021-08-16T09:29:17Z","doi":"10.3390/ijms22168385","year":"2021","acknowledgement":"Open access funding provided by Medical University of Vienna. The authors would like to thank all the participants and health professionals involved in the present study. We want to thank our technical assistants Barbara Widmar and Matthias Witzmann-Stern for their diligent work and constant assistance. We would like to thank Simon Hippenmeyer for access to\r\nbioinformatic infrastructure and resources.","date_created":"2021-08-15T22:01:27Z","citation":{"apa":"Yotova, I., Hudson, Q. J., Pauler, F., Proestling, K., Haslinger, I., Kuessel, L., … Wenzl, R. (2021). LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms22168385\">https://doi.org/10.3390/ijms22168385</a>","ista":"Yotova I, Hudson QJ, Pauler F, Proestling K, Haslinger I, Kuessel L, Perricos A, Husslein H, Wenzl R. 2021. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. 22(16), 8385.","mla":"Yotova, Iveta, et al. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” <i>International Journal of Molecular Sciences</i>, vol. 22, no. 16, 8385, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/ijms22168385\">10.3390/ijms22168385</a>.","chicago":"Yotova, Iveta, Quanah J. Hudson, Florian Pauler, Katharina Proestling, Isabella Haslinger, Lorenz Kuessel, Alexandra Perricos, Heinrich Husslein, and René Wenzl. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” <i>International Journal of Molecular Sciences</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/ijms22168385\">https://doi.org/10.3390/ijms22168385</a>.","short":"I. Yotova, Q.J. Hudson, F. Pauler, K. Proestling, I. Haslinger, L. Kuessel, A. Perricos, H. Husslein, R. Wenzl, International Journal of Molecular Sciences 22 (2021).","ieee":"I. Yotova <i>et al.</i>, “LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line,” <i>International Journal of Molecular Sciences</i>, vol. 22, no. 16. MDPI, 2021.","ama":"Yotova I, Hudson QJ, Pauler F, et al. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. <i>International Journal of Molecular Sciences</i>. 2021;22(16). doi:<a href=\"https://doi.org/10.3390/ijms22168385\">10.3390/ijms22168385</a>"},"article_number":"8385","date_published":"2021-08-04T00:00:00Z","publisher":"MDPI","volume":22,"quality_controlled":"1","department":[{"_id":"SiHi"}],"publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"abstract":[{"text":"Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.","lang":"eng"}],"external_id":{"isi":["000689147400001"]},"language":[{"iso":"eng"}],"publication":"International Journal of Molecular Sciences","article_processing_charge":"Yes","issue":"16","date_updated":"2023-08-11T10:34:13Z","oa":1,"title":"LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line","isi":1,"has_accepted_license":"1","scopus_import":"1","intvolume":"        22","type":"journal_article","status":"public","author":[{"first_name":"Iveta","full_name":"Yotova, Iveta","last_name":"Yotova"},{"last_name":"Hudson","full_name":"Hudson, Quanah J.","first_name":"Quanah J."},{"orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian"},{"full_name":"Proestling, Katharina","first_name":"Katharina","last_name":"Proestling"},{"full_name":"Haslinger, Isabella","first_name":"Isabella","last_name":"Haslinger"},{"first_name":"Lorenz","full_name":"Kuessel, Lorenz","last_name":"Kuessel"},{"first_name":"Alexandra","full_name":"Perricos, Alexandra","last_name":"Perricos"},{"last_name":"Husslein","full_name":"Husslein, Heinrich","first_name":"Heinrich"},{"first_name":"René","full_name":"Wenzl, René","last_name":"Wenzl"}],"publication_identifier":{"issn":["16616596"],"eissn":["14220067"]},"month":"08","file":[{"relation":"main_file","content_type":"application/pdf","file_size":2646018,"access_level":"open_access","creator":"asandaue","date_created":"2021-08-16T09:29:17Z","date_updated":"2021-08-16T09:29:17Z","success":1,"file_name":"2021_InternationalJournalOfMolecularSciences_Yotova.pdf","checksum":"be7f0042607ca60549cb27513c19c6af","file_id":"9922"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"04","oa_version":"Published Version"},{"has_accepted_license":"1","title":"Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration","article_processing_charge":"No","date_updated":"2023-09-22T09:58:30Z","oa":1,"language":[{"iso":"eng"}],"file":[{"date_updated":"2022-09-03T22:30:04Z","date_created":"2021-08-30T09:17:39Z","checksum":"66b56f5b988b233dc66a4f4b4fb2cdfe","file_id":"9971","file_name":"Thesis_Hansen.docx","file_size":10629190,"relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","embargo_to":"open_access","creator":"ahansen"},{"date_updated":"2022-09-03T22:30:04Z","date_created":"2021-08-30T09:29:44Z","checksum":"204fa40321a1c6289b68c473634c4bf3","file_name":"Thesis_Hansen_PDFA-1a.pdf","file_id":"9972","embargo":"2022-09-02","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_size":13457469,"creator":"ahansen"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"02","oa_version":"Published Version","publication_identifier":{"issn":["2663-337X"]},"month":"09","author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","first_name":"Andi H","full_name":"Hansen, Andi H"}],"status":"public","type":"dissertation","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","related_material":{"record":[{"status":"public","id":"8569","relation":"part_of_dissertation"},{"status":"public","id":"960","relation":"part_of_dissertation"}]},"keyword":["Neuronal migration","Non-cell-autonomous","Cell-autonomous","Neurodevelopmental disease"],"date_created":"2021-08-29T12:36:50Z","citation":{"apa":"Hansen, A. H. (2021). <i>Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:9962\">https://doi.org/10.15479/at:ista:9962</a>","mla":"Hansen, Andi H. <i>Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:9962\">10.15479/at:ista:9962</a>.","ista":"Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria.","chicago":"Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:9962\">https://doi.org/10.15479/at:ista:9962</a>.","ama":"Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:9962\">10.15479/at:ista:9962</a>","ieee":"A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration,” Institute of Science and Technology Austria, 2021.","short":"A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration, Institute of Science and Technology Austria, 2021."},"year":"2021","doi":"10.15479/at:ista:9962","_id":"9962","file_date_updated":"2022-09-03T22:30:04Z","abstract":[{"lang":"eng","text":"The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration."}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"publication_status":"published","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"page":"182","date_published":"2021-09-02T00:00:00Z","supervisor":[{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon"}],"publisher":"Institute of Science and Technology Austria","project":[{"grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration"}]},{"article_type":"original","_id":"8569","file_date_updated":"2020-09-28T13:11:17Z","doi":"10.3389/fcell.2020.574382","year":"2020","acknowledgement":"AH was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA Grant Agreement No. 618444 to SH.","citation":{"apa":"Hansen, A. H., &#38; Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental Biology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fcell.2020.574382\">https://doi.org/10.3389/fcell.2020.574382</a>","ieee":"A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex,” <i>Frontiers in Cell and Developmental Biology</i>, vol. 8, no. 9. Frontiers, 2020.","ama":"Hansen AH, Hippenmeyer S. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental Biology</i>. 2020;8(9). doi:<a href=\"https://doi.org/10.3389/fcell.2020.574382\">10.3389/fcell.2020.574382</a>","short":"A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology 8 (2020).","chicago":"Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers in Cell and Developmental Biology</i>. Frontiers, 2020. <a href=\"https://doi.org/10.3389/fcell.2020.574382\">https://doi.org/10.3389/fcell.2020.574382</a>.","mla":"Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers in Cell and Developmental Biology</i>, vol. 8, no. 9, 574382, Frontiers, 2020, doi:<a href=\"https://doi.org/10.3389/fcell.2020.574382\">10.3389/fcell.2020.574382</a>.","ista":"Hansen AH, Hippenmeyer S. 2020. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 8(9), 574382."},"date_created":"2020-09-26T06:11:07Z","related_material":{"record":[{"status":"public","id":"9962","relation":"dissertation_contains"}]},"article_number":"574382","ec_funded":1,"project":[{"name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425"}],"date_published":"2020-09-25T00:00:00Z","publisher":"Frontiers","quality_controlled":"1","volume":8,"department":[{"_id":"SiHi"}],"publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"abstract":[{"text":"Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell–cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future.","lang":"eng"}],"external_id":{"isi":["000577915900001"],"pmid":["33102480"]},"language":[{"iso":"eng"}],"publication":"Frontiers in Cell and Developmental Biology","issue":"9","article_processing_charge":"Yes (via OA deal)","date_updated":"2024-03-25T23:30:23Z","oa":1,"title":"Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex","isi":1,"intvolume":"         8","scopus_import":"1","has_accepted_license":"1","type":"journal_article","status":"public","pmid":1,"author":[{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H"},{"first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"publication_identifier":{"issn":["2296-634X"]},"month":"09","file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_size":5527139,"creator":"dernst","date_updated":"2020-09-28T13:11:17Z","date_created":"2020-09-28T13:11:17Z","checksum":"01f731824194c94c81a5da360d997073","file_name":"2020_Frontiers_Hansen.pdf","file_id":"8584","success":1}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"25","oa_version":"Published Version"},{"status":"public","type":"journal_article","file":[{"access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_size":7835833,"creator":"dernst","date_updated":"2020-12-10T14:07:24Z","date_created":"2020-12-10T14:07:24Z","file_id":"8938","checksum":"92818c23ecc70e35acfa671f3cfb9909","file_name":"2020_AdvScience_Tian.pdf","success":1}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","day":"04","publication_identifier":{"issn":["2198-3844"]},"month":"11","author":[{"first_name":"Anhao","full_name":"Tian, Anhao","last_name":"Tian"},{"full_name":"Kang, Bo","first_name":"Bo","last_name":"Kang"},{"last_name":"Li","full_name":"Li, Baizhou","first_name":"Baizhou"},{"last_name":"Qiu","first_name":"Biying","full_name":"Qiu, Biying"},{"full_name":"Jiang, Wenhong","first_name":"Wenhong","last_name":"Jiang"},{"last_name":"Shao","first_name":"Fangjie","full_name":"Shao, Fangjie"},{"last_name":"Gao","full_name":"Gao, Qingqing","first_name":"Qingqing"},{"first_name":"Rui","full_name":"Liu, Rui","last_name":"Liu"},{"first_name":"Chengwei","full_name":"Cai, Chengwei","last_name":"Cai"},{"full_name":"Jing, Rui","first_name":"Rui","last_name":"Jing"},{"last_name":"Wang","full_name":"Wang, Wei","first_name":"Wei"},{"last_name":"Chen","full_name":"Chen, Pengxiang","first_name":"Pengxiang"},{"full_name":"Liang, Qinghui","first_name":"Qinghui","last_name":"Liang"},{"first_name":"Lili","full_name":"Bao, Lili","last_name":"Bao"},{"full_name":"Man, Jianghong","first_name":"Jianghong","last_name":"Man"},{"last_name":"Wang","first_name":"Yan","full_name":"Wang, Yan"},{"last_name":"Shi","first_name":"Yu","full_name":"Shi, Yu"},{"last_name":"Li","first_name":"Jin","full_name":"Li, Jin"},{"first_name":"Minmin","full_name":"Yang, Minmin","last_name":"Yang"},{"last_name":"Wang","full_name":"Wang, Lisha","first_name":"Lisha"},{"first_name":"Jianmin","full_name":"Zhang, Jianmin","last_name":"Zhang"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon"},{"first_name":"Junming","full_name":"Zhu, Junming","last_name":"Zhu"},{"last_name":"Bian","first_name":"Xiuwu","full_name":"Bian, Xiuwu"},{"first_name":"Ying‐Jie","full_name":"Wang, Ying‐Jie","last_name":"Wang"},{"last_name":"Liu","full_name":"Liu, Chong","first_name":"Chong"}],"publication":"Advanced Science","language":[{"iso":"eng"}],"intvolume":"         7","has_accepted_license":"1","isi":1,"title":"Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting","article_processing_charge":"No","issue":"21","oa":1,"date_updated":"2023-08-22T09:53:01Z","volume":7,"quality_controlled":"1","department":[{"_id":"SiHi"}],"date_published":"2020-11-04T00:00:00Z","publisher":"Wiley","project":[{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020"}],"abstract":[{"text":"Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma.","lang":"eng"}],"external_id":{"isi":["000573860700001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"publication_status":"published","doi":"10.1002/advs.202001724","article_type":"original","_id":"8592","file_date_updated":"2020-12-10T14:07:24Z","article_number":"2001724","ec_funded":1,"keyword":["General Engineering","General Physics and Astronomy","General Materials Science","Medicine (miscellaneous)","General Chemical Engineering","Biochemistry","Genetics and Molecular Biology (miscellaneous)"],"citation":{"apa":"Tian, A., Kang, B., Li, B., Qiu, B., Jiang, W., Shao, F., … Liu, C. (2020). Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. <i>Advanced Science</i>. Wiley. <a href=\"https://doi.org/10.1002/advs.202001724\">https://doi.org/10.1002/advs.202001724</a>","mla":"Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” <i>Advanced Science</i>, vol. 7, no. 21, 2001724, Wiley, 2020, doi:<a href=\"https://doi.org/10.1002/advs.202001724\">10.1002/advs.202001724</a>.","chicago":"Tian, Anhao, Bo Kang, Baizhou Li, Biying Qiu, Wenhong Jiang, Fangjie Shao, Qingqing Gao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” <i>Advanced Science</i>. Wiley, 2020. <a href=\"https://doi.org/10.1002/advs.202001724\">https://doi.org/10.1002/advs.202001724</a>.","ista":"Tian A, Kang B, Li B, Qiu B, Jiang W, Shao F, Gao Q, Liu R, Cai C, Jing R, Wang W, Chen P, Liang Q, Bao L, Man J, Wang Y, Shi Y, Li J, Yang M, Wang L, Zhang J, Hippenmeyer S, Zhu J, Bian X, Wang Y, Liu C. 2020. Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. 7(21), 2001724.","ama":"Tian A, Kang B, Li B, et al. Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. <i>Advanced Science</i>. 2020;7(21). doi:<a href=\"https://doi.org/10.1002/advs.202001724\">10.1002/advs.202001724</a>","ieee":"A. Tian <i>et al.</i>, “Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting,” <i>Advanced Science</i>, vol. 7, no. 21. Wiley, 2020.","short":"A. Tian, B. Kang, B. Li, B. Qiu, W. Jiang, F. Shao, Q. Gao, R. Liu, C. Cai, R. Jing, W. Wang, P. Chen, Q. Liang, L. Bao, J. Man, Y. Wang, Y. Shi, J. Li, M. Yang, L. Wang, J. Zhang, S. Hippenmeyer, J. Zhu, X. Bian, Y. Wang, C. Liu, Advanced Science 7 (2020)."},"date_created":"2020-10-01T09:44:13Z","year":"2020","acknowledgement":"The authors thank Drs. J. Eisen, QR. Lu, S. Duan, Z‐H. Li, W. Mo, and Q. Wu for their critical comments on the manuscript. They also thank Dr. H. Zong for providing the CKO_NG2‐CreER model. This work is supported by the National Key Research and Development Program of China, Stem Cell and Translational Research (2016YFA0101201 to C.L., 2016YFA0100303 to Y.J.W.), the National Natural Science Foundation of China (81673035 and 81972915 to C.L., 81472722 to Y.J.W.), the Science Foundation for Distinguished Young Scientists of Zhejiang Province (LR17H160001 to C.L.), Fundamental Research Funds for the Central Universities (2016QNA7023 and 2017QNA7028 to C.L.) and the Thousand Talent Program for Young Outstanding Scientists, China (to C.L.), IST Austria institutional funds (to S.H.), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (725780 LinPro to S.H.). C.L. is a scholar of K. C. Wong Education Foundation."},{"project":[{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020"}],"publisher":"Cold Spring Harbor Laboratory","date_published":"2020-09-15T00:00:00Z","status":"public","type":"preprint","department":[{"_id":"SiHi"}],"author":[{"full_name":"Gao, Xiaofei","first_name":"Xiaofei","last_name":"Gao"},{"last_name":"Li","full_name":"Li, Jun-Liszt","first_name":"Jun-Liszt"},{"last_name":"Chen","full_name":"Chen, Xingjun","first_name":"Xingjun"},{"last_name":"Ci","full_name":"Ci, Bo","first_name":"Bo"},{"first_name":"Fei","full_name":"Chen, Fei","last_name":"Chen"},{"full_name":"Lu, Nannan","first_name":"Nannan","last_name":"Lu"},{"last_name":"Shen","full_name":"Shen, Bo","first_name":"Bo"},{"last_name":"Zheng","full_name":"Zheng, Lijun","first_name":"Lijun"},{"last_name":"Jia","first_name":"Jie-Min","full_name":"Jia, Jie-Min"},{"last_name":"Yi","full_name":"Yi, Yating","first_name":"Yating"},{"last_name":"Zhang","full_name":"Zhang, Shiwen","first_name":"Shiwen"},{"first_name":"Ying-Chao","full_name":"Shi, Ying-Chao","last_name":"Shi"},{"last_name":"Shi","first_name":"Kaibin","full_name":"Shi, Kaibin"},{"last_name":"Propson","first_name":"Nicholas E","full_name":"Propson, Nicholas E"},{"last_name":"Huang","full_name":"Huang, Yubin","first_name":"Yubin"},{"last_name":"Poinsatte","full_name":"Poinsatte, Katherine","first_name":"Katherine"},{"last_name":"Zhang","full_name":"Zhang, Zhaohuan","first_name":"Zhaohuan"},{"full_name":"Yue, Yuanlei","first_name":"Yuanlei","last_name":"Yue"},{"last_name":"Bosco","first_name":"Dale B","full_name":"Bosco, Dale B"},{"last_name":"Lu","full_name":"Lu, Ying-mei","first_name":"Ying-mei"},{"last_name":"Yang","full_name":"Yang, Shi-bing","first_name":"Shi-bing"},{"last_name":"Adams","full_name":"Adams, Ralf H.","first_name":"Ralf H."},{"first_name":"Volkhard","full_name":"Lindner, Volkhard","last_name":"Lindner"},{"full_name":"Huang, Fen","first_name":"Fen","last_name":"Huang"},{"first_name":"Long-Jun","full_name":"Wu, Long-Jun","last_name":"Wu"},{"full_name":"Zheng, Hui","first_name":"Hui","last_name":"Zheng"},{"first_name":"Feng","full_name":"Han, Feng","last_name":"Han"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon"},{"full_name":"Stowe, Ann M.","first_name":"Ann M.","last_name":"Stowe"},{"first_name":"Bo","full_name":"Peng, Bo","last_name":"Peng"},{"full_name":"Margeta, Marta","first_name":"Marta","last_name":"Margeta"},{"last_name":"Wang","first_name":"Xiaoqun","full_name":"Wang, Xiaoqun"},{"first_name":"Qiang","full_name":"Liu, Qiang","last_name":"Liu"},{"last_name":"Körbelin","first_name":"Jakob","full_name":"Körbelin, Jakob"},{"first_name":"Martin","full_name":"Trepel, Martin","last_name":"Trepel"},{"first_name":"Hui","full_name":"Lu, Hui","last_name":"Lu"},{"last_name":"Zhou","first_name":"Bo O.","full_name":"Zhou, Bo O."},{"last_name":"Zhao","first_name":"Hu","full_name":"Zhao, Hu"},{"full_name":"Su, Wenzhi","first_name":"Wenzhi","last_name":"Su"},{"full_name":"Bachoo, Robert M.","first_name":"Robert M.","last_name":"Bachoo"},{"last_name":"Ge","full_name":"Ge, Woo-ping","first_name":"Woo-ping"}],"publication_status":"submitted","month":"09","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.09.15.262782"}],"oa_version":"Preprint","day":"15","abstract":[{"lang":"eng","text":"The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal <jats:italic>in vivo</jats:italic> imaging, we reported that a substantial proportion of blood vessels in the adult brain sporadically occluded and regressed. Their regression proceeded through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels were found to be widespread in mouse, monkey and human brains. Both brief occlusions of the middle cerebral artery and lipopolysaccharide-mediated inflammation induced an increase of vessel regression. Blockage of leukocyte adhesion to endothelial cells alleviated LPS-induced vessel regression. We further revealed that blood vessel regression caused a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8616","language":[{"iso":"eng"}],"publication":"bioRxiv","doi":"10.1101/2020.09.15.262782","oa":1,"acknowledgement":"The project was initiated in the Jan lab at UCSF. We thank Lily Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing MADM-7 mice and Rolf A Brekken for VEGF-antibodies.  Drs. Yuanquan Song (UPenn), Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics, Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion. Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.) for critical reading. We acknowledge the assistance of the CIBR Imaging core. We also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.; National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key Research and Development Program of China (2016YFE0125400)to F.H.;National Natural Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865) to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670 and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780 to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking Outside the Box Award.","date_updated":"2021-01-12T08:20:19Z","year":"2020","article_processing_charge":"No","title":"Reduction of neuronal activity mediated by blood-vessel regression in the brain","citation":{"apa":"Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (n.d.). Reduction of neuronal activity mediated by blood-vessel regression in the brain. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.09.15.262782\">https://doi.org/10.1101/2020.09.15.262782</a>","ieee":"X. Gao <i>et al.</i>, “Reduction of neuronal activity mediated by blood-vessel regression in the brain,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","ama":"Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel regression in the brain. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.09.15.262782\">10.1101/2020.09.15.262782</a>","short":"X. Gao, J.-L. Li, X. Chen, B. Ci, F. Chen, N. Lu, B. Shen, L. Zheng, J.-M. Jia, Y. Yi, S. Zhang, Y.-C. Shi, K. Shi, N.E. Propson, Y. Huang, K. Poinsatte, Z. Zhang, Y. Yue, D.B. Bosco, Y. Lu, S. Yang, R.H. Adams, V. Lindner, F. Huang, L.-J. Wu, H. Zheng, F. Han, S. Hippenmeyer, A.M. Stowe, B. Peng, M. Margeta, X. Wang, Q. Liu, J. Körbelin, M. Trepel, H. Lu, B.O. Zhou, H. Zhao, W. Su, R.M. Bachoo, W. Ge, BioRxiv (n.d.).","chicago":"Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.09.15.262782\">https://doi.org/10.1101/2020.09.15.262782</a>.","mla":"Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.09.15.262782\">10.1101/2020.09.15.262782</a>.","ista":"Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y, Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Su W, Bachoo RM, Ge W. Reduction of neuronal activity mediated by blood-vessel regression in the brain. bioRxiv, <a href=\"https://doi.org/10.1101/2020.09.15.262782\">10.1101/2020.09.15.262782</a>."},"date_created":"2020-10-06T08:58:59Z","ec_funded":1},{"pmid":1,"publisher":"Cold Spring Harbor Laboratory","date_published":"2020-11-05T00:00:00Z","type":"preprint","status":"public","department":[{"_id":"SiHi"}],"month":"11","oa_version":"Preprint","main_file_link":[{"url":"https://doi.org/10.1101/2020.11.03.366948","open_access":"1"}],"day":"05","external_id":{"pmid":["PPR234457 "]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation."}],"author":[{"full_name":"Santini, Laura","first_name":"Laura","last_name":"Santini"},{"first_name":"Florian","full_name":"Halbritter, Florian","last_name":"Halbritter"},{"full_name":"Titz-Teixeira, Fabian","first_name":"Fabian","last_name":"Titz-Teixeira"},{"last_name":"Suzuki","first_name":"Toru","full_name":"Suzuki, Toru"},{"last_name":"Asami","full_name":"Asami, Maki","first_name":"Maki"},{"last_name":"Ramesmayer","first_name":"Julia","full_name":"Ramesmayer, Julia"},{"last_name":"Ma","full_name":"Ma, Xiaoyan","first_name":"Xiaoyan"},{"last_name":"Lackner","first_name":"Andreas","full_name":"Lackner, Andreas"},{"first_name":"Nick","full_name":"Warr, Nick","last_name":"Warr"},{"first_name":"Florian","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"first_name":"Simon","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ernest","full_name":"Laue, Ernest","last_name":"Laue"},{"last_name":"Farlik","full_name":"Farlik, Matthias","first_name":"Matthias"},{"last_name":"Bock","full_name":"Bock, Christoph","first_name":"Christoph"},{"last_name":"Beyer","first_name":"Andreas","full_name":"Beyer, Andreas"},{"last_name":"Perry","full_name":"Perry, Anthony C. F.","first_name":"Anthony C. F."},{"full_name":"Leeb, Martin","first_name":"Martin","last_name":"Leeb"}],"publication_status":"submitted","publication":"bioRxiv","doi":"10.1101/2020.11.03.366948","language":[{"iso":"eng"}],"_id":"8813","oa":1,"date_updated":"2023-09-12T11:05:28Z","article_processing_charge":"No","year":"2020","title":"Novel imprints in mouse blastocysts are predominantly DNA methylation independent","citation":{"ieee":"L. Santini <i>et al.</i>, “Novel imprints in mouse blastocysts are predominantly DNA methylation independent,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","ama":"Santini L, Halbritter F, Titz-Teixeira F, et al. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.11.03.366948\">10.1101/2020.11.03.366948</a>","short":"L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, J. Ramesmayer, X. Ma, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik, C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, BioRxiv (n.d.).","chicago":"Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Julia Ramesmayer, Xiaoyan Ma, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.11.03.366948\">https://doi.org/10.1101/2020.11.03.366948</a>.","ista":"Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ramesmayer J, Ma X, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer A, Perry ACF, Leeb M. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv, <a href=\"https://doi.org/10.1101/2020.11.03.366948\">10.1101/2020.11.03.366948</a>.","mla":"Santini, Laura, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.11.03.366948\">10.1101/2020.11.03.366948</a>.","apa":"Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ramesmayer, J., … Leeb, M. (n.d.). Novel imprints in mouse blastocysts are predominantly DNA methylation independent. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.11.03.366948\">https://doi.org/10.1101/2020.11.03.366948</a>"},"date_created":"2020-11-26T07:17:19Z"},{"status":"public","type":"journal_article","month":"12","publication_identifier":{"issn":["2073-4409"]},"day":"11","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"relation":"main_file","access_level":"open_access","file_size":3504525,"content_type":"application/pdf","creator":"dernst","date_updated":"2020-12-14T08:09:43Z","date_created":"2020-12-14T08:09:43Z","checksum":"5095cbdc728c9a510c5761cf60a8861c","file_name":"2020_Cells_Zhang.pdf","file_id":"8950","success":1}],"author":[{"full_name":"Zhang, Xuying","first_name":"Xuying","last_name":"Zhang"},{"first_name":"Christine V.","full_name":"Mennicke, Christine V.","last_name":"Mennicke"},{"last_name":"Xiao","first_name":"Guanxi","full_name":"Xiao, Guanxi"},{"first_name":"Robert J","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie"},{"last_name":"Haider","first_name":"Mansoor","full_name":"Haider, Mansoor"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon"},{"last_name":"Ghashghaei","full_name":"Ghashghaei, H. Troy","first_name":"H. Troy"}],"publication":"Cells","language":[{"iso":"eng"}],"isi":1,"intvolume":"         9","has_accepted_license":"1","oa":1,"date_updated":"2023-08-24T10:57:48Z","issue":"12","article_processing_charge":"No","title":"Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage","publisher":"MDPI","date_published":"2020-12-11T00:00:00Z","department":[{"_id":"SiHi"}],"volume":9,"quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"ddc":["570"],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"external_id":{"isi":["000601787300001"]},"abstract":[{"lang":"eng","text":"<jats:p>Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis.</jats:p>"}],"publication_status":"published","doi":"10.3390/cells9122662","file_date_updated":"2020-12-14T08:09:43Z","_id":"8949","article_type":"original","ec_funded":1,"article_number":"2662","acknowledgement":"This research was funded by grants from the National Institutes of Health to H.T.G. (R01NS098370 and R01NS089795). C.V.M. was supported by a National Science Foundation Graduate Research Fellowship (DGE-1746939). R.B. was supported by the FWF Lise-Meitner program (M 2416), and S.H. was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 725780 LinPro).The authors thank members of the Ghashghaei lab for discussions, technical support, and help with preparation of the manuscript.","year":"2020","citation":{"apa":"Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer, S., &#38; Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. <i>Cells</i>. MDPI. <a href=\"https://doi.org/10.3390/cells9122662\">https://doi.org/10.3390/cells9122662</a>","short":"X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer, H.T. Ghashghaei, Cells 9 (2020).","ama":"Zhang X, Mennicke CV, Xiao G, et al. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. <i>Cells</i>. 2020;9(12). doi:<a href=\"https://doi.org/10.3390/cells9122662\">10.3390/cells9122662</a>","ieee":"X. Zhang <i>et al.</i>, “Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,” <i>Cells</i>, vol. 9, no. 12. MDPI, 2020.","mla":"Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” <i>Cells</i>, vol. 9, no. 12, 2662, MDPI, 2020, doi:<a href=\"https://doi.org/10.3390/cells9122662\">10.3390/cells9122662</a>.","chicago":"Zhang, Xuying, Christine V. Mennicke, Guanxi Xiao, Robert J Beattie, Mansoor Haider, Simon Hippenmeyer, and H. Troy Ghashghaei. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” <i>Cells</i>. MDPI, 2020. <a href=\"https://doi.org/10.3390/cells9122662\">https://doi.org/10.3390/cells9122662</a>.","ista":"Zhang X, Mennicke CV, Xiao G, Beattie RJ, Haider M, Hippenmeyer S, Ghashghaei HT. 2020. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. 9(12), 2662."},"date_created":"2020-12-14T08:04:03Z"},{"has_accepted_license":"1","intvolume":"         1","article_processing_charge":"No","issue":"3","oa":1,"date_updated":"2021-01-12T08:21:36Z","title":"Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy","publication":"STAR Protocols","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2666-1667"]},"month":"12","file":[{"creator":"dernst","access_level":"open_access","relation":"main_file","file_size":4031449,"content_type":"application/pdf","success":1,"file_id":"8996","checksum":"f1e9a433e9cb0f41f7b6df6b76db1f6e","file_name":"2020_STARProtocols_Laukoter.pdf","date_created":"2021-01-07T15:57:27Z","date_updated":"2021-01-07T15:57:27Z"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","day":"18","author":[{"last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","full_name":"Laukoter, Susanne"},{"first_name":"Nicole","full_name":"Amberg, Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207"},{"full_name":"Pauler, Florian","first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon"}],"status":"public","type":"journal_article","pmid":1,"article_number":"100215","ec_funded":1,"year":"2020","acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical Facilities (PCF). N.A received support from the FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 to S.H.; NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","citation":{"chicago":"Laukoter, Susanne, Nicole Amberg, Florian Pauler, and Simon Hippenmeyer. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” <i>STAR Protocols</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">https://doi.org/10.1016/j.xpro.2020.100215</a>.","ista":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. 2020. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. STAR Protocols. 1(3), 100215.","mla":"Laukoter, Susanne, et al. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” <i>STAR Protocols</i>, vol. 1, no. 3, 100215, Elsevier, 2020, doi:<a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">10.1016/j.xpro.2020.100215</a>.","ieee":"S. Laukoter, N. Amberg, F. Pauler, and S. Hippenmeyer, “Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy,” <i>STAR Protocols</i>, vol. 1, no. 3. Elsevier, 2020.","ama":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. <i>STAR Protocols</i>. 2020;1(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">10.1016/j.xpro.2020.100215</a>","short":"S. Laukoter, N. Amberg, F. Pauler, S. Hippenmeyer, STAR Protocols 1 (2020).","apa":"Laukoter, S., Amberg, N., Pauler, F., &#38; Hippenmeyer, S. (2020). Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2020.100215\">https://doi.org/10.1016/j.xpro.2020.100215</a>"},"date_created":"2020-12-30T10:17:07Z","doi":"10.1016/j.xpro.2020.100215","_id":"8978","article_type":"original","file_date_updated":"2021-01-07T15:57:27Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"ddc":["570"],"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables concomitant fluorescent cell labeling and induction of uniparental chromosome disomy (UPD) with single-cell resolution. In UPD, imprinted genes are either overexpressed 2-fold or are not expressed. Here, the MADM platform is utilized to probe imprinting phenotypes at the transcriptional level. This protocol highlights major steps for the generation and isolation of projection neurons and astrocytes with MADM-induced UPD from mouse cerebral cortex for downstream single-cell and low-input sample RNA-sequencing experiments.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Laukoter et al. (2020b)."}],"external_id":{"pmid":["33377108"]},"publication_status":"published","date_published":"2020-12-18T00:00:00Z","publisher":"Elsevier","volume":1,"quality_controlled":"1","department":[{"_id":"SiHi"}],"project":[{"_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression"},{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F07805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"}]},{"author":[{"orcid":"0000-0002-7903-3010","last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne","full_name":"Laukoter, Susanne"},{"first_name":"Robert J","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie"},{"first_name":"Florian","full_name":"Pauler, Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048"},{"orcid":"0000-0002-3183-8207","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","first_name":"Nicole"},{"last_name":"Nakayama","first_name":"Keiichi I.","full_name":"Nakayama, Keiichi I."},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"month":"01","publication_identifier":{"issn":["2041-1723"]},"oa_version":"Published Version","day":"10","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"date_created":"2020-01-13T07:42:31Z","date_updated":"2020-07-14T12:47:54Z","file_id":"7261","checksum":"ebf1ed522f4e0be8d94c939c1806a709","file_name":"2020_NatureComm_Laukoter.pdf","content_type":"application/pdf","file_size":8063333,"access_level":"open_access","relation":"main_file","creator":"dernst"}],"type":"journal_article","status":"public","oa":1,"date_updated":"2023-08-17T14:23:41Z","article_processing_charge":"No","title":"Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development","isi":1,"intvolume":"        11","scopus_import":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"publication":"Nature Communications","publication_status":"published","ddc":["570"],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"external_id":{"isi":["000551459000005"]},"abstract":[{"lang":"eng","text":"The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype."}],"project":[{"name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031"},{"grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex"},{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"}],"publisher":"Springer Nature","date_published":"2020-01-10T00:00:00Z","department":[{"_id":"SiHi"}],"quality_controlled":"1","volume":11,"year":"2020","date_created":"2020-01-11T10:42:48Z","citation":{"short":"S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020).","ama":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-019-14077-2\">10.1038/s41467-019-14077-2</a>","ieee":"S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer, “Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020.","ista":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 11, 195.","mla":"Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” <i>Nature Communications</i>, vol. 11, 195, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-019-14077-2\">10.1038/s41467-019-14077-2</a>.","chicago":"Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-019-14077-2\">https://doi.org/10.1038/s41467-019-14077-2</a>.","apa":"Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., &#38; Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-019-14077-2\">https://doi.org/10.1038/s41467-019-14077-2</a>"},"ec_funded":1,"article_number":"195","related_material":{"link":[{"url":"https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/","description":"News on IST Homepage","relation":"press_release"}]},"file_date_updated":"2020-07-14T12:47:54Z","_id":"7253","article_type":"original","acknowledged_ssus":[{"_id":"PreCl"}],"doi":"10.1038/s41467-019-14077-2"},{"file_date_updated":"2020-09-24T07:03:20Z","_id":"7593","article_type":"original","doi":"10.7554/elife.51512","citation":{"ama":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.51512\">10.7554/elife.51512</a>","ieee":"H. M. Moon, S. Hippenmeyer, L. Luo, and A. Wynshaw-Boris, “LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","short":"H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020).","chicago":"Moon, Hyang Mi, Simon Hippenmeyer, Liqun Luo, and Anthony Wynshaw-Boris. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.51512\">https://doi.org/10.7554/elife.51512</a>.","ista":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. 2020. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. eLife. 9, 51512.","mla":"Moon, Hyang Mi, et al. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” <i>ELife</i>, vol. 9, 51512, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.51512\">10.7554/elife.51512</a>.","apa":"Moon, H. M., Hippenmeyer, S., Luo, L., &#38; Wynshaw-Boris, A. (2020). LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.51512\">https://doi.org/10.7554/elife.51512</a>"},"date_created":"2020-03-20T13:16:41Z","year":"2020","article_number":"51512","department":[{"_id":"SiHi"}],"volume":9,"quality_controlled":"1","publisher":"eLife Sciences Publications","date_published":"2020-03-11T00:00:00Z","publication_status":"published","external_id":{"isi":["000522835800001"],"pmid":["32159512"]},"abstract":[{"lang":"eng","text":"Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation."}],"ddc":["570"],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}],"publication":"eLife","title":"LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility","oa":1,"date_updated":"2023-08-18T07:06:31Z","article_processing_charge":"No","scopus_import":"1","intvolume":"         9","has_accepted_license":"1","isi":1,"pmid":1,"status":"public","type":"journal_article","author":[{"last_name":"Moon","first_name":"Hyang Mi","full_name":"Moon, Hyang Mi"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon"},{"last_name":"Luo","full_name":"Luo, Liqun","first_name":"Liqun"},{"first_name":"Anthony","full_name":"Wynshaw-Boris, Anthony","last_name":"Wynshaw-Boris"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/751958"}],"day":"11","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"date_updated":"2020-09-24T07:03:20Z","date_created":"2020-09-24T07:03:20Z","checksum":"396ceb2dd10b102ef4e699666b9342c3","file_id":"8567","file_name":"2020_elife_Moon.pdf","success":1,"relation":"main_file","file_size":15089438,"access_level":"open_access","content_type":"application/pdf","creator":"dernst"}],"publication_identifier":{"issn":["2050-084X"]},"month":"03"}]