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Chromatin accessibility dynamics in a model of human forebrain development.


ABSTRACT: Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at different developmental stages. We used this resource to map genetic risk for disease and to explore evolutionary conservation. Moreover, we integrated chromatin accessibility with transcriptomics to identify putative enhancer-gene linkages and transcription factors that regulate human corticogenesis. Overall, this platform brings insights into gene-regulatory dynamics at previously inaccessible stages of human forebrain development, including signatures of neuropsychiatric disorders.

SUBMITTER: Trevino AE 

PROVIDER: S-EPMC7313757 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Chromatin accessibility dynamics in a model of human forebrain development.

Trevino Alexandro E AE   Sinnott-Armstrong Nasa N   Andersen Jimena J   Yoon Se-Jin SJ   Huber Nina N   Pritchard Jonathan K JK   Chang Howard Y HY   Greenleaf William J WJ   Pașca Sergiu P SP  

Science (New York, N.Y.) 20200101 6476


Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at  ...[more]

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