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Chromatin accessibility during human first-trimester neurodevelopment

Medicine and Health

Chromatin accessibility during human first-trimester neurodevelopment

C. C. A. Mannens, L. Hu, et al.

Explore groundbreaking insights into early brain development with a high-resolution multiomic atlas of chromatin accessibility and gene expression, crafted by an exemplary team of researchers including Camiel C. A. Mannens, Lijuan Hu, and Peter Lönnerberg. Discover how transcription factors and regulatory elements play pivotal roles, revealing vulnerabilities in GABAergic neurons linked to major depressive disorder.

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Playback language: English
Abstract
This study presents a high-resolution multiomic atlas of chromatin accessibility and gene expression in the first-trimester human brain. The researchers defined 135 cell clusters, linked *cis*-regulatory elements to gene expression, and identified transcription factor binding sites. A convolutional neural network predicted neuronal subtypes, elucidating the activation mechanism of *ESRRB* in Purkinje cells. Linking disease-associated SNPs to *cis*-regulatory elements revealed midbrain-derived GABAergic neurons as particularly vulnerable to major depressive disorder-related mutations. This work offers insights into gene regulatory mechanisms during early brain development and provides a reference for future studies.
Publisher
Nature
Published On
May 01, 2024
Authors
Camiel C. A. Mannens, Lijuan Hu, Peter Lönnerberg, Marijn Schipper, Caleb C. Reagor, Xiaofei Li, Xiaoling He, Roger A. Barker, Erik Sundström, Danielle Posthuma, Sten Linnarsson
Tags
chromatin accessibility
gene expression
neurodevelopment
transcription factors
major depressive disorder
cis-regulatory elements
neuronal subtypes
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