Transcriptomic and epigenomic dynamics associated with development of human iPSC-derived GABAergic interneurons
Abstract GABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Identification of the genetic regulatory elements and transcription factors that contribute toward GIN fun...
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Published in | Human molecular genetics Vol. 29; no. 15; pp. 2579 - 2595 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
29.08.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract
GABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Identification of the genetic regulatory elements and transcription factors that contribute toward GIN function may provide new insight into the pathways underlying proper GIN activity while also indicating potential therapeutic targets for GIN-associated disorders, such as schizophrenia and epilepsy. In this study, we examined the temporal changes in gene expression and chromatin accessibility during GIN development by performing transcriptomic and epigenomic analyses on human induced pluripotent stem cell-derived neurons at 22, 50 and 78 days (D) post-differentiation. We observed 13 221 differentially accessible regions (DARs) of chromatin that associate with temporal changes in gene expression at D78 and D50, relative to D22. We also classified families of transcription factors that are increasingly enriched at DARs during differentiation, indicating regulatory networks that likely drive GIN development. Collectively, these data provide a resource for examining the molecular networks regulating GIN functionality. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA. |
ISSN: | 0964-6906 1460-2083 |
DOI: | 10.1093/hmg/ddaa150 |