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Kronprinsessan Lovisas f\u00f6rening f\u00f6r barnasjukv\u00e5rd och Stiftelsen Axel Tielmans minnesfond"},{"name":"Swedish Foundation for Medical Research"},{"name":"The Foundations of Petrus och Augusta Hedlund"},{"name":"The Strategic Research Area Neuroscience (StratNeuro) at Karolinska Institutet"},{"DOI":"10.13039\/501100001728","name":"The Swedish Foundation for International Cooperation in Research and Higher Education","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001728","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Committee for Research at Karolinska Institutet","award":["R35GM128661"],"award-info":[{"award-number":["R35GM128661"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35GM128661"],"award-info":[{"award-number":["R35GM128661"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Karolinska Institute: Karolinska Institutet"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Genetic variants affecting Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU) have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role of HNRNPU in cerebral cortical development, but the effects of HNRNPU deficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes of HNRNPU locus deficiency during in vitro neural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate that HNRNPU deficiency leads to chromatin remodeling of A\/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level HNRNPU downregulation leads to an increased fraction of neural progenitors in the maturing neuronal population. We conclude that the HNRNPU locus is involved in delayed commitment of neural progenitors to differentiate in cell types with hindbrain profile.<\/jats:p>","DOI":"10.1242\/bio.060113","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T10:05:22Z","timestamp":1696932322000},"source":"Crossref","is-referenced-by-count":22,"title":["Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis"],"prefix":"10.1242","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-2446","authenticated-orcid":false,"given":"Francesca","family":"Mastropasqua","sequence":"first","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-4282","authenticated-orcid":false,"given":"Marika","family":"Oksanen","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Soldini","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 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University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-4417","authenticated-orcid":false,"given":"Abishek","family":"Arora","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-0940","authenticated-orcid":false,"given":"Roberto","family":"Ballarino","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 3 Department of Microbiology, Tumor and Cell Biology , , 17164 Stockholm , Sweden"},{"name":"Science for Life Laboratory 4 , Tomtebodav\u00e4gen 23A, 17165 Solna , Sweden"},{"name":"Karolinska Institutet 5 Department of Medical Biochemistry and Biophysics , , 17165 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Molinari","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 6 Department of Neuroscience , , 17176 Solna , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5453-2737","authenticated-orcid":false,"given":"Federico","family":"Agostini","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory 4 , Tomtebodav\u00e4gen 23A, 17165 Solna , Sweden"},{"name":"Karolinska Institutet 5 Department of Medical Biochemistry and Biophysics , , 17165 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-8960","authenticated-orcid":false,"given":"Axel","family":"Poulet","sequence":"additional","affiliation":[{"name":"Yale University 7 Department of Molecular, Cellular and Developmental Biology , , New Haven, CT 06511 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-3429","authenticated-orcid":false,"given":"Michelle","family":"Watts","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-4115","authenticated-orcid":false,"given":"Ielyzaveta","family":"Rabkina","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8442-4246","authenticated-orcid":false,"given":"Martin","family":"Becker","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-6645","authenticated-orcid":false,"given":"Danyang","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of 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Solna , Sweden"},{"name":"Lund University 11 Lund Stem Cell Center , , 22100 Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-6978","authenticated-orcid":false,"given":"Nicola","family":"Crosetto","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 3 Department of Microbiology, Tumor and Cell Biology , , 17164 Stockholm , Sweden"},{"name":"Science for Life Laboratory 4 , Tomtebodav\u00e4gen 23A, 17165 Solna , Sweden"},{"name":"Human Technopole 12 , Viale Rita Levi-Montalcini 1, 20157 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-9082","authenticated-orcid":false,"given":"Magda","family":"Bienko","sequence":"additional","affiliation":[{"name":"Karolinska Institutet 3 Department of Microbiology, Tumor and Cell Biology , , 17164 Stockholm , Sweden"},{"name":"Science for Life Laboratory 4 , Tomtebodav\u00e4gen 23A, 17165 Solna , 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Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":"Karolinska Institute, Region Stockholm 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , Sweden"},{"name":", Karolinska University Hospital, Region Stockholm 2 Astrid Lindgren Children's Hospital , 17164 Stockholm , Sweden"},{"name":", Curtin School of Allied Health, Curtin University 13 Curtin Autism Research Group , 6845 Perth , Western Australia"},{"name":", Stockholm Health Care Services, Region Stockholm 14 Child and Adolescent Psychiatry , 10431 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-4697","authenticated-orcid":false,"given":"Kristiina","family":"Tammimies","sequence":"additional","affiliation":[{"name":"Centre for Psychiatry Research 1 Center of Neurodevelopmental Disorders (KIND) , , Department of Women's and Children's Health , , 17164 Stockholm , 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