[{"publication_identifier":{"eissn":["2753-149X"]},"publication_status":"published","file_date_updated":"2023-08-16T08:00:30Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general.","lang":"eng"}],"intvolume":"         1","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"has_accepted_license":"1","article_type":"original","date_created":"2022-02-25T07:52:11Z","volume":1,"oa_version":"Published Version","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","author":[{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","last_name":"Hansen","first_name":"Andi H"},{"last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048"},{"orcid":"0000-0003-4844-6311","first_name":"Michael","last_name":"Riedl","full_name":"Riedl, Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"last_name":"Heger","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","full_name":"Heger, Anna-Magdalena","first_name":"Anna-Magdalena"},{"orcid":"0000-0002-7903-3010","first_name":"Susanne","last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","first_name":"Armel"},{"id":"3A374330-F248-11E8-B48F-1D18A9856A87","full_name":"Hof, Björn","last_name":"Hof","first_name":"Björn","orcid":"0000-0003-2057-2754"},{"first_name":"Li Huei","last_name":"Tsai","full_name":"Tsai, Li Huei"},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"day":"07","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"1","citation":{"chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford Academic, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford Academic, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford Academic. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>","ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford Academic, 2022."},"language":[{"iso":"eng"}],"oa":1,"file":[{"file_size":4846551,"date_created":"2023-08-16T08:00:30Z","creator":"dernst","date_updated":"2023-08-16T08:00:30Z","file_id":"14061","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"822e76e056c07099d1fb27d1ece5941b"}],"article_number":"kvac009","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"month":"07","quality_controlled":"1","ddc":["570"],"type":"journal_article","date_updated":"2023-11-30T10:55:12Z","_id":"10791","publisher":"Oxford Academic","doi":"10.1093/oons/kvac009","article_processing_charge":"No","acknowledgement":"A.H.H. 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 S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","date_published":"2022-07-07T00:00:00Z","ec_funded":1,"project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"status":"public","publication":"Oxford Open Neuroscience","related_material":{"record":[{"id":"12726","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"14530"}]},"year":"2022"},{"publication":"Neurochemistry International","status":"public","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"}],"ec_funded":1,"pmid":1,"date_published":"2021-05-01T00:00:00Z","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.","isi":1,"year":"2021","external_id":{"pmid":["33600873"],"isi":["000635575000005"]},"keyword":["Cell Biology","Cellular and Molecular Neuroscience"],"ddc":["570"],"quality_controlled":"1","article_processing_charge":"Yes (via OA deal)","doi":"10.1016/j.neuint.2021.104986","publisher":"Elsevier","_id":"9188","date_updated":"2023-08-07T13:48:26Z","type":"journal_article","oa":1,"language":[{"iso":"eng"}],"citation":{"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).","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>","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>","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>.","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.","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>."},"issue":"5","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"05","department":[{"_id":"SiHi"}],"article_number":"104986","file":[{"date_created":"2021-08-11T12:30:38Z","file_size":7083499,"creator":"kschuh","date_updated":"2021-08-11T12:30:38Z","file_id":"9883","success":1,"file_name":"2021_NCI_Pauler.pdf","access_level":"open_access","content_type":"application/pdf","relation":"main_file","checksum":"c6d7a40089cd29e289f9b22e75768304"}],"has_accepted_license":"1","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"intvolume":"       145","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"}],"file_date_updated":"2021-08-11T12:30:38Z","publication_identifier":{"issn":["0197-0186"]},"publication_status":"published","day":"01","scopus_import":"1","author":[{"full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian"},{"last_name":"Hudson","full_name":"Hudson, Quanah","first_name":"Quanah"},{"first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"title":"Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond","oa_version":"Published Version","volume":145,"date_created":"2021-02-23T12:31:43Z","article_type":"original"},{"language":[{"iso":"eng"}],"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"short":"S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher, T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.","ieee":"S. Laukoter <i>et al.</i>, “Cell-type specificity of genomic imprinting in cerebral cortex,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.","ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. 2020;107(6):1160-1179.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>.","apa":"Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>","ista":"Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T, Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 107(6), 1160–1179.e9.","chicago":"Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>."},"issue":"6","month":"09","file":[{"relation":"main_file","checksum":"7becdc16a6317304304631087ae7dd7f","success":1,"file_name":"2020_Neuron_Laukoter.pdf","access_level":"open_access","content_type":"application/pdf","file_id":"8828","file_size":8911830,"date_created":"2020-12-02T09:26:46Z","date_updated":"2020-12-02T09:26:46Z","creator":"dernst"}],"department":[{"_id":"SiHi"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"abstract":[{"text":"In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity.","lang":"eng"}],"intvolume":"       107","has_accepted_license":"1","file_date_updated":"2020-12-02T09:26:46Z","publication_status":"published","publication_identifier":{"issn":["0896-6273"]},"oa_version":"Published Version","title":"Cell-type specificity of genomic imprinting in cerebral cortex","day":"23","scopus_import":"1","author":[{"first_name":"Susanne","orcid":"0000-0002-7903-3010","last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","full_name":"Beattie, Robert J","last_name":"Beattie","first_name":"Robert J","orcid":"0000-0002-8483-8753"},{"orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen","first_name":"Andi H"},{"first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher"},{"first_name":"Thomas","last_name":"Penz","full_name":"Penz, Thomas"},{"last_name":"Bock","full_name":"Bock, Christoph","orcid":"0000-0001-6091-3088","first_name":"Christoph"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"date_created":"2020-07-23T16:03:12Z","article_type":"original","volume":107,"status":"public","publication":"Neuron","project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002"},{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"date_published":"2020-09-23T00:00:00Z","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo for comments on earlier versions of the manuscript. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031). R.B. received support from the FWF Meitner-Programm (M 2416). This work was also supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 618444 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.","ec_funded":1,"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/","description":"News on IST Website"}]},"external_id":{"isi":["000579698700006"]},"year":"2020","isi":1,"ddc":["570"],"page":"1160-1179.e9","quality_controlled":"1","publisher":"Elsevier","article_processing_charge":"No","doi":"10.1016/j.neuron.2020.06.031","type":"journal_article","_id":"8162","date_updated":"2023-08-22T08:20:11Z"},{"article_type":"original","date_created":"2020-12-30T10:17:07Z","volume":1,"title":"Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy","oa_version":"Published Version","author":[{"first_name":"Susanne","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter"},{"orcid":"0000-0002-3183-8207","first_name":"Nicole","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"}],"day":"18","publication_identifier":{"issn":["2666-1667"]},"publication_status":"published","file_date_updated":"2021-01-07T15:57:27Z","intvolume":"         1","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"abstract":[{"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).","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"has_accepted_license":"1","article_number":"100215","file":[{"relation":"main_file","checksum":"f1e9a433e9cb0f41f7b6df6b76db1f6e","success":1,"file_name":"2020_STARProtocols_Laukoter.pdf","access_level":"open_access","content_type":"application/pdf","file_id":"8996","date_created":"2021-01-07T15:57:27Z","file_size":4031449,"date_updated":"2021-01-07T15:57:27Z","creator":"dernst"}],"department":[{"_id":"SiHi"}],"month":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"3","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>.","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>","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).","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."},"language":[{"iso":"eng"}],"oa":1,"type":"journal_article","date_updated":"2021-01-12T08:21:36Z","_id":"8978","publisher":"Elsevier","doi":"10.1016/j.xpro.2020.100215","article_processing_charge":"No","quality_controlled":"1","ddc":["570"],"external_id":{"pmid":["33377108"]},"year":"2020","date_published":"2020-12-18T00:00:00Z","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.","pmid":1,"ec_funded":1,"project":[{"_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","grant_number":"T0101031"},{"grant_number":"F07805","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020"}],"status":"public","publication":"STAR Protocols"},{"external_id":{"isi":["000551459000005"]},"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"}]},"isi":1,"year":"2020","project":[{"_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","grant_number":"T0101031"},{"name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"publication":"Nature Communications","status":"public","date_published":"2020-01-10T00:00:00Z","ec_funded":1,"publisher":"Springer Nature","doi":"10.1038/s41467-019-14077-2","article_processing_charge":"No","type":"journal_article","date_updated":"2023-08-17T14:23:41Z","_id":"7253","ddc":["570"],"quality_controlled":"1","month":"01","article_number":"195","file":[{"access_level":"open_access","content_type":"application/pdf","file_name":"2020_NatureComm_Laukoter.pdf","checksum":"ebf1ed522f4e0be8d94c939c1806a709","relation":"main_file","creator":"dernst","date_updated":"2020-07-14T12:47:54Z","file_size":8063333,"date_created":"2020-01-13T07:42:31Z","file_id":"7261"}],"department":[{"_id":"SiHi"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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>.","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>","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>.","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.","short":"S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020).","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.","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>"},"oa_version":"Published Version","title":"Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development","author":[{"orcid":"0000-0002-7903-3010","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"last_name":"Beattie","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","first_name":"Robert J"},{"last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","orcid":"0000-0002-7462-0048"},{"orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole"},{"first_name":"Keiichi I.","full_name":"Nakayama, Keiichi I.","last_name":"Nakayama"},{"first_name":"Simon","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"}],"day":"10","scopus_import":"1","article_type":"original","date_created":"2020-01-11T10:42:48Z","volume":11,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"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.","lang":"eng"}],"intvolume":"        11","acknowledged_ssus":[{"_id":"PreCl"}],"has_accepted_license":"1","publication_identifier":{"issn":["2041-1723"]},"publication_status":"published","file_date_updated":"2020-07-14T12:47:54Z"},{"external_id":{"isi":["000462680200002"]},"year":"2019","isi":1,"project":[{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"publication":"Journal of Neurochemistry","status":"public","date_published":"2019-04-01T00:00:00Z","acknowledgement":" This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung \r\nn[f+b]   (C13-002)   to   SH;   a   program   grant   from   the   Human   Frontiers   Science   Program (RGP0053/2014)  to SH;  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, and the  European  Research  Council  (ERC)  under  the  European  Union’s  Horizon  2020  research  and innovation programme (grant agreement No 725780 LinPro)to SH.\r\n","ec_funded":1,"publisher":"Wiley","doi":"10.1111/jnc.14601","article_processing_charge":"Yes (via OA deal)","type":"journal_article","date_updated":"2023-09-11T13:40:26Z","_id":"27","ddc":["570"],"page":"12-26","quality_controlled":"1","month":"04","file":[{"file_size":889709,"date_created":"2020-01-07T13:35:52Z","creator":"kschuh","date_updated":"2020-07-14T12:45:45Z","file_id":"7239","file_name":"2019_Wiley_Amberg.pdf","access_level":"open_access","content_type":"application/pdf","relation":"main_file","checksum":"db027721a95d36f5de36aadcd0bdf7e6"}],"department":[{"_id":"SiHi"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","issue":"1","citation":{"ieee":"N. Amberg, S. Laukoter, and S. Hippenmeyer, “Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex,” <i>Journal of Neurochemistry</i>, vol. 149, no. 1. Wiley, pp. 12–26, 2019.","short":"N. Amberg, S. Laukoter, S. Hippenmeyer, Journal of Neurochemistry 149 (2019) 12–26.","ama":"Amberg N, Laukoter S, Hippenmeyer S. Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex. <i>Journal of Neurochemistry</i>. 2019;149(1):12-26. doi:<a href=\"https://doi.org/10.1111/jnc.14601\">10.1111/jnc.14601</a>","apa":"Amberg, N., Laukoter, S., &#38; Hippenmeyer, S. (2019). Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex. <i>Journal of Neurochemistry</i>. Wiley. <a href=\"https://doi.org/10.1111/jnc.14601\">https://doi.org/10.1111/jnc.14601</a>","mla":"Amberg, Nicole, et al. “Epigenetic Cues Modulating the Generation of Cell Type Diversity in the Cerebral Cortex.” <i>Journal of Neurochemistry</i>, vol. 149, no. 1, Wiley, 2019, pp. 12–26, doi:<a href=\"https://doi.org/10.1111/jnc.14601\">10.1111/jnc.14601</a>.","chicago":"Amberg, Nicole, Susanne Laukoter, and Simon Hippenmeyer. “Epigenetic Cues Modulating the Generation of Cell Type Diversity in the Cerebral Cortex.” <i>Journal of Neurochemistry</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/jnc.14601\">https://doi.org/10.1111/jnc.14601</a>.","ista":"Amberg N, Laukoter S, Hippenmeyer S. 2019. Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex. Journal of Neurochemistry. 149(1), 12–26."},"title":"Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex","oa_version":"Published Version","author":[{"first_name":"Nicole","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"orcid":"0000-0002-7903-3010","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","full_name":"Laukoter, Susanne","last_name":"Laukoter"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer"}],"scopus_import":"1","day":"01","article_type":"review","date_created":"2018-12-11T11:44:14Z","volume":149,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"       149","abstract":[{"lang":"eng","text":"The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved."}],"has_accepted_license":"1","publication_status":"published","file_date_updated":"2020-07-14T12:45:45Z"},{"degree_awarded":"PhD","status":"public","date_published":"2018-11-21T00:00:00Z","year":"2018","publist_id":"8046","page":"1 - 139","ddc":["570"],"alternative_title":["ISTA Thesis"],"article_processing_charge":"No","doi":"10.15479/AT:ISTA:th1057","publisher":"Institute of Science and Technology Austria","_id":"10","date_updated":"2023-09-07T12:40:44Z","type":"dissertation","oa":1,"pubrep_id":"1057","language":[{"iso":"eng"}],"citation":{"ama":"Laukoter S. Role of genomic imprinting in cerebral cortex development. 2018:1-139. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1057\">10.15479/AT:ISTA:th1057</a>","ieee":"S. Laukoter, “Role of genomic imprinting in cerebral cortex development,” Institute of Science and Technology Austria, 2018.","short":"S. Laukoter, Role of Genomic Imprinting in Cerebral Cortex Development, Institute of Science and Technology Austria, 2018.","ista":"Laukoter S. 2018. Role of genomic imprinting in cerebral cortex development. Institute of Science and Technology Austria.","chicago":"Laukoter, Susanne. “Role of Genomic Imprinting in Cerebral Cortex Development.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th1057\">https://doi.org/10.15479/AT:ISTA:th1057</a>.","apa":"Laukoter, S. (2018). <i>Role of genomic imprinting in cerebral cortex development</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th1057\">https://doi.org/10.15479/AT:ISTA:th1057</a>","mla":"Laukoter, Susanne. <i>Role of Genomic Imprinting in Cerebral Cortex Development</i>. Institute of Science and Technology Austria, 2018, pp. 1–139, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1057\">10.15479/AT:ISTA:th1057</a>."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","supervisor":[{"id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","full_name":"Vicoso, Beatriz","last_name":"Vicoso","orcid":"0000-0002-4579-8306","first_name":"Beatriz"}],"month":"11","department":[{"_id":"SiHi"}],"file":[{"file_name":"Thesis_LaukoterSusanne_FINAL.docx","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","checksum":"41fdbf5fdce312802935d88a8ad9932c","file_size":17949175,"date_created":"2019-05-10T07:47:04Z","creator":"dernst","date_updated":"2019-11-23T23:30:03Z","file_id":"6396","embargo_to":"open_access"},{"file_name":"Thesis_LaukoterSusanne_FINAL.pdf","access_level":"open_access","content_type":"application/pdf","relation":"main_file","checksum":"53001a9a0c9e570e598d861bb0af28aa","file_size":21187245,"date_created":"2019-05-10T07:47:04Z","date_updated":"2021-02-11T11:17:16Z","creator":"dernst","embargo":"2019-11-21","file_id":"6397"}],"has_accepted_license":"1","abstract":[{"text":"Genomic imprinting is an epigenetic process that leads to parent of origin-specific gene expression in a subset of genes. Imprinted genes are essential for brain development, and deregulation of imprinting is associated with neurodevelopmental diseases and the pathogenesis of psychiatric disorders. However, the cell-type specificity of imprinting at single cell resolution, and how imprinting and thus gene dosage regulates neuronal circuit assembly is still largely unknown. Here, MADM (Mosaic Analysis with Double Markers) technology was employed to assess genomic imprinting at single cell level. By visualizing MADM-induced uniparental disomies (UPDs) in distinct colors at single cell level in genetic mosaic animals, this experimental paradigm provides a unique quantitative platform to systematically assay the UPD-mediated imbalances in imprinted gene expression at unprecedented resolution. An experimental pipeline based on FACS, RNA-seq and bioinformatics analysis was established and applied to systematically map cell-type-specific ‘imprintomes’ in the mouse brain. The results revealed that parental-specific expression of imprinted genes per se is rarely cell-type-specific even at the individual cell level. Conversely, when we extended the comparison to downstream responses resulting from imbalanced imprinted gene expression, we discovered an unexpectedly high degree of cell-type specificity. Furthermore, we determined a novel function of genomic imprinting in cortical astrocyte production and in olfactory bulb (OB) granule cell generation. These results suggest important functional implication of genomic imprinting for generating cell-type diversity in the brain. In addition, MADM provides a powerful tool to study candidate genes by concomitant genetic manipulation and fluorescent labelling of single cells. MADM-based candidate gene approach was utilized to identify potential imprinted genes involved in the generation of cortical astrocytes and OB granule cells. We investigated p57Kip2, a maternally expressed gene and known cell cycle regulator. Although we found that p57Kip2 does not play a role in these processes, we detected an unexpected function of the paternal allele previously thought to be silent. Finally, we took advantage of a key property of MADM which is to allow unambiguous investigation of environmental impact on single cells. The experimental pipeline based on FACS and RNA-seq analysis of MADM-labeled cells was established to probe the functional differences of single cell loss of gene function compared to global loss of function on a transcriptional level. With this method, both common and distinct responses were isolated due to cell-autonomous and non-autonomous effects acting on genotypically identical cells. As a result, transcriptional changes were identified which result solely from the surrounding environment. Using the MADM technology to study genomic imprinting at single cell resolution, we have identified cell-type-specific gene expression, novel gene function and the impact of environment on single cell transcriptomes. Together, these provide important insights to the understanding of mechanisms regulating cell-type specificity and thus diversity in the brain.","lang":"eng"}],"file_date_updated":"2021-02-11T11:17:16Z","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"day":"21","author":[{"first_name":"Susanne","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter"}],"oa_version":"Published Version","title":"Role of genomic imprinting in cerebral cortex development","date_created":"2018-12-11T11:44:08Z"},{"publisher":"Cell Press","article_processing_charge":"No","doi":"10.1016/j.neuron.2017.04.012","type":"journal_article","_id":"944","date_updated":"2023-09-26T15:37:02Z","page":"517 - 533.e3","quality_controlled":"1","external_id":{"isi":["000400466700011"]},"year":"2017","isi":1,"publist_id":"6473","publication":"Neuron","status":"public","project":[{"grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"}],"date_published":"2017-05-03T00:00:00Z","ec_funded":1,"title":"Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells","oa_version":"None","day":"03","scopus_import":"1","author":[{"orcid":"0000-0002-8483-8753","first_name":"Robert J","last_name":"Beattie","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","full_name":"Beattie, Robert J"},{"first_name":"Maria P","id":"2C67902A-F248-11E8-B48F-1D18A9856A87","full_name":"Postiglione, Maria P","last_name":"Postiglione"},{"first_name":"Laura","orcid":"0000-0002-8937-410X","last_name":"Burnett","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","full_name":"Burnett, Laura"},{"first_name":"Susanne","orcid":"0000-0002-7903-3010","last_name":"Laukoter","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","first_name":"Carmen"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian"},{"first_name":"Guanxi","full_name":"Xiao, Guanxi","last_name":"Xiao"},{"first_name":"Olga","last_name":"Klezovitch","full_name":"Klezovitch, Olga"},{"last_name":"Vasioukhin","full_name":"Vasioukhin, Valeri","first_name":"Valeri"},{"last_name":"Ghashghaei","full_name":"Ghashghaei, Troy","first_name":"Troy"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"date_created":"2018-12-11T11:49:20Z","volume":94,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"text":"The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.","lang":"eng"}],"intvolume":"        94","publication_status":"published","publication_identifier":{"issn":["08966273"]},"month":"05","department":[{"_id":"SiHi"},{"_id":"MaJö"}],"language":[{"iso":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Beattie RJ, Postiglione MP, Burnett L, et al. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. 2017;94(3):517-533.e3. doi:<a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">10.1016/j.neuron.2017.04.012</a>","short":"R.J. Beattie, M.P. Postiglione, L. Burnett, S. Laukoter, C. Streicher, F. Pauler, G. Xiao, O. Klezovitch, V. Vasioukhin, T. Ghashghaei, S. Hippenmeyer, Neuron 94 (2017) 517–533.e3.","ieee":"R. J. Beattie <i>et al.</i>, “Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells,” <i>Neuron</i>, vol. 94, no. 3. Cell Press, p. 517–533.e3, 2017.","chicago":"Beattie, Robert J, Maria P Postiglione, Laura Burnett, Susanne Laukoter, Carmen Streicher, Florian Pauler, Guanxi Xiao, et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">https://doi.org/10.1016/j.neuron.2017.04.012</a>.","ista":"Beattie RJ, Postiglione MP, Burnett L, Laukoter S, Streicher C, Pauler F, Xiao G, Klezovitch O, Vasioukhin V, Ghashghaei T, Hippenmeyer S. 2017. Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. Neuron. 94(3), 517–533.e3.","mla":"Beattie, Robert J., et al. “Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells.” <i>Neuron</i>, vol. 94, no. 3, Cell Press, 2017, p. 517–533.e3, doi:<a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">10.1016/j.neuron.2017.04.012</a>.","apa":"Beattie, R. J., Postiglione, M. P., Burnett, L., Laukoter, S., Streicher, C., Pauler, F., … Hippenmeyer, S. (2017). Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells. <i>Neuron</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.neuron.2017.04.012\">https://doi.org/10.1016/j.neuron.2017.04.012</a>"},"issue":"3"}]