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

Neha Tiwari, Abhijeet Pataskar, Sophie Péron, Sudhir Thakurela, Sanjeeb Kumar Sahu, María Figueres-Oñate, Nicolás Marichal, Laura López-Mascaraque, Vijay K. Tiwari, Benedikt Berninger

Research output: Contribution to journalArticle

7 Citations (Scopus)
187 Downloads (Pure)

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. Neural stem cells give rise to both neurons and glia. Modeling gliogenesis in vitro, Tiwari et al. show that the generation of astrocytes involves several transcriptionally and epigenetically distinct stages. The authors found that the transcription factors NFIA, ATF3, and RUNX2 play pivotal roles in establishing these stages.
Original languageEnglish
Pages (from-to)557-571.e8
Number of pages24
JournalCell Stem Cell
Volume23
Issue number4
Early online date04 Oct 2018
DOIs
Publication statusPublished - 04 Oct 2018

Keywords

  • astrocyte
  • astrogliogenesis
  • cell fate
  • epigenetic mechanisms
  • gene regulation
  • neural stem cells
  • neurogenesis
  • transcription factors

Fingerprint Dive into the research topics of 'Stage-Specific Transcription Factors Drive Astrogliogenesis by Remodeling Gene Regulatory Landscapes'. Together they form a unique fingerprint.

  • Cite this

    Tiwari, N., Pataskar, A., Péron, S., Thakurela, S., Sahu, S. K., Figueres-Oñate, M., Marichal, N., López-Mascaraque, L., Tiwari, V. K., & Berninger, B. (2018). Stage-Specific Transcription Factors Drive Astrogliogenesis by Remodeling Gene Regulatory Landscapes. Cell Stem Cell, 23(4), 557-571.e8. https://doi.org/10.1016/j.stem.2018.09.008