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Shapira, Y.* ; Noack, F. ; Vangelisti, S. ; Chong, F. ; Lifshitz, A.* ; Tanay, A. ; Bonev, B.

Neural stem cell epigenomes and fate bias are temporally coordinated during mouse cortical development.

Genes Dev., DOI: 10.1101/gad.353090.125 (2026)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
During cortical development, neural stem cells (NSCs) combine self-renewal with the sequential production of different subtypes of projection neurons as well as glia cells. How the NSC epigenome accommodates this over time remains unresolved. Here, we address this gap by multimodal epigenomic profiling of mouse cortical development across six time points and five embryonic days. Single-cell gene expression and temporal modeling reveal that NSC self-renewal is not homeostatic, showing progressively stronger astrocytic preference over time. Chromosome accessibility, DNA methylation, and Hi-C show that this process involves major reorganization of the NSC epigenome. A model combining transcription factor motif affinities with epigenetic features, as well as integration of the results with a reporter assay in vivo, show that activation of the NSC neuronal fate regulatory program may be affected by a changing epigenome. Collectively, our findings uncover temporal epigenomic reprogramming that underlies the evolving differentiation potential of NSCs, providing insights into the intrinsic and extrinsic mechanisms that pattern cortical lineages.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Brain Development ; Computational Modeling ; Epigenetics ; In Vivo Mpra ; Single-cell Omics
ISSN (print) / ISBN 0890-9369
e-ISSN 1549-5477
Zeitschrift Genes and Development
Verlag Cold Spring Harbor Laboratory Press
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Brain Epigenomics (BEG)
Institute of Epigenetics and Stem Cells (IES)