[{"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","citation":{"mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022)."},"ec_funded":1,"author":[{"last_name":"Villa","full_name":"Villa, Carlo Emanuele","first_name":"Carlo Emanuele"},{"full_name":"Cheroni, Cristina","first_name":"Cristina","last_name":"Cheroni"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter"},{"first_name":"Alejandro","full_name":"López-Tóbon, Alejandro","last_name":"López-Tóbon"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","first_name":"Bárbara","last_name":"Oliveira"},{"last_name":"Sacco","full_name":"Sacco, Roberto","first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Aysan Çerağ","full_name":"Yahya, Aysan Çerağ","last_name":"Yahya","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"last_name":"Gabriele","first_name":"Michele","full_name":"Gabriele, Michele"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","last_name":"Tavakoli","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba"},{"full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"last_name":"Gabitto","full_name":"Gabitto, Mariano","first_name":"Mariano"},{"last_name":"Danzl","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"full_name":"Testa, Giuseppe","first_name":"Giuseppe","last_name":"Testa"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"type":"journal_article","day":"05","related_material":{"record":[{"id":"12364","relation":"dissertation_contains","status":"public"}]},"pmid":1,"project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF","_id":"2690FEAC-B435-11E9-9278-68D0E5697425"}],"acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","doi":"10.1016/j.celrep.2022.110615","ddc":["570"],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"language":[{"iso":"eng"}],"date_created":"2022-04-15T09:03:10Z","month":"04","isi":1,"publisher":"Elsevier","intvolume":"        39","status":"public","publication":"Cell Reports","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"quality_controlled":"1","year":"2022","has_accepted_license":"1","oa_version":"Published Version","article_type":"original","publication_identifier":{"issn":["2211-1247"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-03-25T23:30:25Z","article_processing_charge":"Yes","issue":"1","date_published":"2022-04-05T00:00:00Z","_id":"11160","abstract":[{"lang":"eng","text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling."}],"file":[{"content_type":"application/pdf","file_id":"11164","relation":"main_file","date_created":"2022-04-15T09:06:25Z","success":1,"file_name":"2022_CellReports_Villa.pdf","creator":"dernst","file_size":"7808644","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_updated":"2022-04-15T09:06:25Z","access_level":"open_access"}],"article_number":"110615","oa":1,"publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"volume":39,"file_date_updated":"2022-04-15T09:06:25Z"},{"abstract":[{"text":"Loss of functional cardiomyocytes is a major determinant of heart failure after myocardial infarction. Previous high throughput screening studies have identified a few microRNAs (miRNAs) that can induce cardiomyocyte proliferation and stimulate cardiac regeneration in mice. Here, we show that all of the most effective of these miRNAs activate nuclear localization of the master transcriptional cofactor Yes-associated protein (YAP) and induce expression of YAP-responsive genes. In particular, miR-199a-3p directly targets two mRNAs coding for proteins impinging on the Hippo pathway, the upstream YAP inhibitory kinase TAOK1, and the E3 ubiquitin ligase β-TrCP, which leads to YAP degradation. Several of the pro-proliferative miRNAs (including miR-199a-3p) also inhibit filamentous actin depolymerization by targeting Cofilin2, a process that by itself activates YAP nuclear translocation. Thus, activation of YAP and modulation of the actin cytoskeleton are major components of the pro-proliferative action of miR-199a-3p and other miRNAs that induce cardiomyocyte proliferation.","lang":"eng"}],"_id":"7128","date_published":"2019-05-28T00:00:00Z","file":[{"access_level":"open_access","date_updated":"2020-07-14T12:47:50Z","checksum":"c5d855d07263bfec718673385d0ea2d7","file_size":4650750,"creator":"rcubero","file_name":"torrini_cellreports_2019.pdf","date_created":"2019-11-26T22:30:43Z","relation":"main_file","file_id":"7129","content_type":"application/pdf"}],"issue":"9","article_processing_charge":"Yes","volume":27,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"file_date_updated":"2020-07-14T12:47:50Z","oa":1,"publication_status":"published","has_accepted_license":"1","oa_version":"Published Version","year":"2019","article_type":"original","publication_identifier":{"issn":["2211-1247"]},"date_updated":"2021-01-12T08:11:56Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["31141697"]},"date_created":"2019-11-26T22:30:07Z","extern":"1","month":"05","page":"2759-2771.e5","intvolume":"        27","status":"public","quality_controlled":"1","publication":"Cell Reports","publisher":"Elsevier","author":[{"last_name":"Torrini","first_name":"Consuelo","full_name":"Torrini, Consuelo"},{"orcid":"0000-0003-0002-1867","id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J","full_name":"Cubero, Ryan J","last_name":"Cubero"},{"last_name":"Dirkx","full_name":"Dirkx, Ellen","first_name":"Ellen"},{"full_name":"Braga, Luca","first_name":"Luca","last_name":"Braga"},{"last_name":"Ali","full_name":"Ali, Hashim","first_name":"Hashim"},{"last_name":"Prosdocimo","full_name":"Prosdocimo, Giulia","first_name":"Giulia"},{"last_name":"Gutierrez","first_name":"Maria Ines","full_name":"Gutierrez, Maria Ines"},{"last_name":"Collesi","full_name":"Collesi, Chiara","first_name":"Chiara"},{"full_name":"Licastro, Danilo","first_name":"Danilo","last_name":"Licastro"},{"last_name":"Zentilin","first_name":"Lorena","full_name":"Zentilin, Lorena"},{"last_name":"Mano","full_name":"Mano, Miguel","first_name":"Miguel"},{"last_name":"Zacchigna","first_name":"Serena","full_name":"Zacchigna, Serena"},{"full_name":"Vendruscolo, Michele","first_name":"Michele","last_name":"Vendruscolo"},{"last_name":"Marsili","full_name":"Marsili, Matteo","first_name":"Matteo"},{"last_name":"Samal","full_name":"Samal, Areejit","first_name":"Areejit"},{"full_name":"Giacca, Mauro","first_name":"Mauro","last_name":"Giacca"}],"type":"journal_article","day":"28","title":"Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation","citation":{"ista":"Torrini C, Cubero RJ, Dirkx E, Braga L, Ali H, Prosdocimo G, Gutierrez MI, Collesi C, Licastro D, Zentilin L, Mano M, Zacchigna S, Vendruscolo M, Marsili M, Samal A, Giacca M. 2019. Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation. Cell Reports. 27(9), 2759–2771.e5.","ieee":"C. Torrini <i>et al.</i>, “Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation,” <i>Cell Reports</i>, vol. 27, no. 9. Elsevier, p. 2759–2771.e5, 2019.","chicago":"Torrini, Consuelo, Ryan J Cubero, Ellen Dirkx, Luca Braga, Hashim Ali, Giulia Prosdocimo, Maria Ines Gutierrez, et al. “Common Regulatory Pathways Mediate Activity of MicroRNAs Inducing Cardiomyocyte Proliferation.” <i>Cell Reports</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">https://doi.org/10.1016/j.celrep.2019.05.005</a>.","mla":"Torrini, Consuelo, et al. “Common Regulatory Pathways Mediate Activity of MicroRNAs Inducing Cardiomyocyte Proliferation.” <i>Cell Reports</i>, vol. 27, no. 9, Elsevier, 2019, p. 2759–2771.e5, doi:<a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">10.1016/j.celrep.2019.05.005</a>.","short":"C. Torrini, R.J. Cubero, E. Dirkx, L. Braga, H. Ali, G. Prosdocimo, M.I. Gutierrez, C. Collesi, D. Licastro, L. Zentilin, M. Mano, S. Zacchigna, M. Vendruscolo, M. Marsili, A. Samal, M. Giacca, Cell Reports 27 (2019) 2759–2771.e5.","apa":"Torrini, C., Cubero, R. J., Dirkx, E., Braga, L., Ali, H., Prosdocimo, G., … Giacca, M. (2019). Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">https://doi.org/10.1016/j.celrep.2019.05.005</a>","ama":"Torrini C, Cubero RJ, Dirkx E, et al. Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation. <i>Cell Reports</i>. 2019;27(9):2759-2771.e5. doi:<a href=\"https://doi.org/10.1016/j.celrep.2019.05.005\">10.1016/j.celrep.2019.05.005</a>"},"doi":"10.1016/j.celrep.2019.05.005","ddc":["576"],"language":[{"iso":"eng"}],"keyword":["cardiomyocyte","cell cycle","Cofilin2","cytoskeleton","Hippo","microRNA","regeneration","YAP"],"pmid":1},{"extern":"1","month":"12","date_created":"2020-03-21T16:08:18Z","page":"1692-1702","quality_controlled":"1","publication":"Cell Reports","status":"public","intvolume":"         9","publisher":"Elsevier","day":"11","author":[{"id":"2DE75584-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0471-8285","first_name":"Shutang","full_name":"Tan, Shutang","last_name":"Tan"},{"last_name":"Xue","first_name":"Hong-Wei","full_name":"Xue, Hong-Wei"}],"type":"journal_article","citation":{"mla":"Tan, Shutang, and Hong-Wei Xue. “Casein Kinase 1 Regulates Ethylene Synthesis by Phosphorylating and Promoting the Turnover of ACS5.” <i>Cell Reports</i>, vol. 9, no. 5, Elsevier, 2014, pp. 1692–702, doi:<a href=\"https://doi.org/10.1016/j.celrep.2014.10.047\">10.1016/j.celrep.2014.10.047</a>.","chicago":"Tan, Shutang, and Hong-Wei Xue. “Casein Kinase 1 Regulates Ethylene Synthesis by Phosphorylating and Promoting the Turnover of ACS5.” <i>Cell Reports</i>. Elsevier, 2014. <a href=\"https://doi.org/10.1016/j.celrep.2014.10.047\">https://doi.org/10.1016/j.celrep.2014.10.047</a>.","ista":"Tan S, Xue H-W. 2014. Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5. Cell Reports. 9(5), 1692–1702.","ieee":"S. Tan and H.-W. Xue, “Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5,” <i>Cell Reports</i>, vol. 9, no. 5. Elsevier, pp. 1692–1702, 2014.","ama":"Tan S, Xue H-W. Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5. <i>Cell Reports</i>. 2014;9(5):1692-1702. doi:<a href=\"https://doi.org/10.1016/j.celrep.2014.10.047\">10.1016/j.celrep.2014.10.047</a>","apa":"Tan, S., &#38; Xue, H.-W. (2014). Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2014.10.047\">https://doi.org/10.1016/j.celrep.2014.10.047</a>","short":"S. Tan, H.-W. Xue, Cell Reports 9 (2014) 1692–1702."},"title":"Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5","language":[{"iso":"eng"}],"doi":"10.1016/j.celrep.2014.10.047","ddc":["580"],"file":[{"date_created":"2020-03-23T12:23:40Z","relation":"main_file","file_id":"7613","content_type":"application/pdf","access_level":"open_access","date_updated":"2020-07-14T12:48:01Z","checksum":"23c30de4ac98ce9879fc054121517626","creator":"dernst","file_size":2755808,"file_name":"2014_CellPress_Tan.pdf"}],"_id":"7598","date_published":"2014-12-11T00:00:00Z","issue":"5","article_processing_charge":"No","file_date_updated":"2020-07-14T12:48:01Z","volume":9,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"publication_status":"published","oa":1,"article_type":"original","has_accepted_license":"1","oa_version":"Published Version","year":"2014","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T08:14:24Z","publication_identifier":{"issn":["2211-1247"]}}]