{"_id":"11160","file_date_updated":"2022-04-15T09:06:25Z","keyword":["General Biochemistry","Genetics and Molecular Biology"],"author":[{"last_name":"Villa","full_name":"Villa, Carlo Emanuele","first_name":"Carlo Emanuele"},{"last_name":"Cheroni","first_name":"Cristina","full_name":"Cheroni, Cristina"},{"full_name":"Dotter, Christoph","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","orcid":"0000-0002-9033-9096"},{"last_name":"López-Tóbon","first_name":"Alejandro","full_name":"López-Tóbon, Alejandro"},{"full_name":"Oliveira, Bárbara","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","last_name":"Oliveira"},{"first_name":"Roberto","full_name":"Sacco, Roberto","last_name":"Sacco","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Yahya, Aysan Çerağ","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","last_name":"Yahya"},{"first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gabriele","full_name":"Gabriele, Michele","first_name":"Michele"},{"last_name":"Tavakoli","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba"},{"full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"last_name":"Gabitto","full_name":"Gabitto, Mariano","first_name":"Mariano"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G"},{"full_name":"Testa, Giuseppe","first_name":"Giuseppe","last_name":"Testa"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia"}],"day":"05","article_processing_charge":"Yes","license":"https://creativecommons.org/licenses/by/4.0/","doi":"10.1016/j.celrep.2022.110615","file":[{"creator":"dernst","relation":"main_file","date_updated":"2022-04-15T09:06:25Z","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf","success":1,"file_id":"11164","date_created":"2022-04-15T09:06:25Z","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","content_type":"application/pdf","file_size":"7808644"}],"oa":1,"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>.","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.","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>","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.","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).","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>."},"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205"}],"publication":"Cell Reports","volume":39,"article_number":"110615","has_accepted_license":"1","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"type":"journal_article","ddc":["570"],"status":"public","quality_controlled":"1","abstract":[{"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.","lang":"eng"}],"date_updated":"2024-04-23T22:30:43Z","isi":1,"ec_funded":1,"publication_status":"published","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","intvolume":"        39","publisher":"Elsevier","external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"language":[{"iso":"eng"}],"date_published":"2022-04-05T00:00:00Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_created":"2022-04-15T09:03:10Z","issue":"1","oa_version":"Published Version","year":"2022","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.","month":"04","article_type":"original","publication_identifier":{"issn":["2211-1247"]},"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12364"}]},"pmid":1}