Stage-Specific Transcription Factors Drive Astrogliogenesis by Remodeling Gene Regulatory Landscapes.

Cell Stem Cell
Authors
Keywords
Abstract

A broad molecular framework of how neural stem cells are specified toward astrocyte fate during brain development has proven elusive. Here we perform comprehensive and integrated transcriptomic and epigenomic analyses to delineate gene regulatory programs that drive the developmental trajectory from mouse embryonic stem cells to astrocytes. We report molecularly distinct phases of astrogliogenesis that exhibit stage- and lineage-specific transcriptomic and epigenetic signatures with unique primed and active chromatin regions, thereby revealing regulatory elements and transcriptional programs underlying astrocyte generation and maturation. By searching for transcription factors that function at these elements, we identified NFIA and ATF3 as drivers of astrocyte differentiation from neural precursor cells while RUNX2 promotes astrocyte maturation. These transcription factors facilitate stage-specific gene expression programs by switching the chromatin state of their target regulatory elements from primed to active. Altogether, these findings provide integrated insights into the genetic and epigenetic mechanisms steering the trajectory of astrogliogenesis.

Year of Publication
2018
Journal
Cell Stem Cell
Volume
23
Issue
4
Pages
557-571.e8
Date Published
2018 10 04
ISSN
1875-9777
DOI
10.1016/j.stem.2018.09.008
PubMed ID
30290178
PubMed Central ID
PMC6179960
Links
Grant list
206410/Z/17/Z / Wellcome Trust / United Kingdom
MR/N026063/1 / MRC_ / Medical Research Council / United Kingdom
206410/Z/17 / WT_ / Wellcome Trust / United Kingdom