{"id":1631,"date":"2022-10-10T20:06:12","date_gmt":"2022-10-10T20:06:12","guid":{"rendered":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/?page_id=1631"},"modified":"2022-10-10T20:08:45","modified_gmt":"2022-10-10T20:08:45","slug":"ipsc_kcl","status":"publish","type":"page","link":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/ipsc_kcl\/","title":{"rendered":"Activity-dependent transcriptional program in glutamatergic neurons enriched for genetic risk for schizophrenia"},"content":{"rendered":"<p><strong>ABSTRACT:<\/strong> Converging evidence from large-scale genetic and post-mortem studies highlight the role of aberrant neurotransmission and genetic regulation in schizophrenia. To better understand how the activity-dependent regulome contributes to risk for psychiatric disorders, we profile the transcriptomic and epigenomic changes following neuronal depolarization in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons from individuals with schizophrenia and controls. Multi-omic data integration associates global patterns of chromatin accessibility with gene expression and identifies enhancer-promoter interactions in glutamatergic neurons. Within one hour of KCl-induced depolarization, independent of diagnosis, glutamatergic neurons display substantial activity-dependent changes in the expression of genes regulating synaptic function and are linked to schizophrenia and autism spectrum disorder. Depolarization-induced changes in chromatin accessibility likewise reveal significant heritability enrichment for schizophrenia, adding to mounting evidence that sequence variation within activation-dependent regulatory elements contributes to the genetic risk for schizophrenia. Moreover, we identify key drivers within co-expressed modules of both schizophrenia- and activity-associated genes. Overall, we demonstrate that deciphering the activity-dependent regulome in glutamatergic neurons could reveal novel targets for advanced diagnosis and therapy.<\/p>\n<h2>Data access<\/h2>\n<p>Raw and processed data are available at <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE203082\">GEO:GSE203082<\/a>. Additionally, you can view the open chromatin tracks in the <a href=\"http:\/\/genome.ucsc.edu\/cgi-bin\/hgTracks?hubUrl=https:\/\/ipsc-kcl.s3.amazonaws.com\/hub.txt&amp;position=chr6:33418833-33421472\" target=\"_blank\" rel=\"noopener\">UCSC genome browser<\/a>.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>ABSTRACT: Converging evidence from large-scale genetic and post-mortem studies highlight the role of aberrant neurotransmission and genetic regulation in schizophrenia. To better understand how the activity-dependent regulome contributes to risk for psychiatric disorders, we profile the transcriptomic and epigenomic changes following neuronal depolarization in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons from individuals with [&hellip;]<\/p>\n","protected":false},"author":570,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-1631","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/pages\/1631","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/users\/570"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/comments?post=1631"}],"version-history":[{"count":3,"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/pages\/1631\/revisions"}],"predecessor-version":[{"id":1634,"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/pages\/1631\/revisions\/1634"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/roussos-lab\/wp-json\/wp\/v2\/media?parent=1631"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}