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PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics. RNA sequencing of cortical organoids at day 32 unveiled changes in cell adhesion and WNT-signaling pathways. ChIP-seq of PRDM16 identified binding sites in postmortem human fetal cortex, indicating the conservation of PRDM16 binding to developmental genes in mice and humans, potentially at enhancer sites. A shared motif between PRDM16 and LHX2 was identified and further examined through comparison with LHX2 ChIP-seq data from mice. These results suggested a collaborative partnership between PRDM16 and LHX2 in regulating a common set of genes and pathways in cortical radial glia cells, possibly via their synergistic involvement in cortical development.<\/jats:p>","DOI":"10.1093\/oons\/kvae001","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T07:38:17Z","timestamp":1705909097000},"source":"Crossref","is-referenced-by-count":6,"title":["PRDM16 co-operates with LHX2 to shape the human brain"],"prefix":"10.1093","volume":"3","author":[{"given":"Varun","family":"Suresh","sequence":"first","affiliation":[{"name":"Weizmann Institute of Science Department of Molecular Genetics, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Weizmann Institute of Science Department of Molecular Neuroscience, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Tata Institute of Fundamental Research Department of Biological Sciences, , Homi Bhabha Road, Navy Nagar, Colaba, Mumbai 400005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidisha","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science Department of Molecular Genetics, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Weizmann Institute of Science Department of Molecular Neuroscience, , 234 Herzl St., Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami Yair","family":"Tshuva","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science Department of Molecular Genetics, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Weizmann Institute of Science Department of Molecular Neuroscience, , 234 Herzl St., Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miri","family":"Danan Gotthold","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science Department of Molecular Genetics, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Weizmann Institute of Science Department of Molecular Neuroscience, , 234 Herzl St., Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsviya","family":"Olender","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science Department of Molecular Genetics, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Weizmann Institute of Science Department of Molecular Neuroscience, , 234 Herzl St., Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahima","family":"Bose","sequence":"additional","affiliation":[{"name":"Tata Institute of Fundamental Research Department of Biological Sciences, , Homi Bhabha Road, Navy Nagar, Colaba, Mumbai 400005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh J","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Pune Chromatin Biology and Epigenetics Laboratory, Biology Department, , Dr. Homi Bhabha Road, Pune 411008, India"},{"name":"Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter , 3 Dr. Bohr-Gasse, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruria Ben","family":"Zeev","sequence":"additional","affiliation":[{"name":"Tel Aviv University Edmond and Lily Safra Pediatric Hospital, Sheba Medical Center and Tel Aviv School of Medicine, , Ramat Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Scott","family":"Smith","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Department of Pharmacology, , 320 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubha","family":"Tole","sequence":"additional","affiliation":[{"name":"Tata Institute of Fundamental Research Department of Biological Sciences, , Homi Bhabha Road, Navy Nagar, Colaba, Mumbai 400005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Galande","sequence":"additional","affiliation":[{"name":"Indian Institute of Science Education and Research Pune Chromatin Biology and Epigenetics Laboratory, Biology Department, , Dr. Homi Bhabha Road, Pune 411008, India"},{"name":"Center of Excellence in Epigenetics, Shiv Nadar University Department of Life Sciences, , Shiv Nadar IoE, Gautam Buddha Nagar, Uttar Pradesh - 201314, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey C","family":"Harwell","sequence":"additional","affiliation":[{"name":"University of California, San Francisco Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, , 35 Medical Center Way, San Francisco, CA 94143, USA"},{"name":"Weill Institute for Neuroscience , 1651 4th St, San Francisco, CA94158, USA"},{"name":"University of California, San Francisco Department of Neurology, , 505 Parnassus Ave, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Manuel","family":"Baizabal","sequence":"additional","affiliation":[{"name":"Indiana University Department of Biology, , 1001 E 3rd St., Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Reiner","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science Department of Molecular Genetics, , 234 Herzl St., Rehovot 7610001, Israel"},{"name":"Weizmann Institute of Science Department of Molecular Neuroscience, , 234 Herzl St., Rehovot 7610001, 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