Oxygen levels epigenetically regulate fate switching of neural precursor cells via hypoxia-inducible factor 1α-Notch signal interaction in the developing brain

Tetsuji Mutoh, Tsukasa Sanosaka, Kei Ito, Kinichi Nakashima

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Oxygen levels in tissues including the embryonic brain are lower than those in the atmosphere. We reported previously that Notch signal activation induces demethylation of astrocytic genes, conferring astrocyte differentiation ability on midgestational neural precursor cells (mgNPCs). Here, we show that the oxygen sensor hypoxia-inducible factor 1α (HIF1α) plays a critical role in astrocytic gene demethylation in mgNPCs by cooperating with the Notch signaling pathway. Expression of constitutively active HIF1α and a hyperoxic environment, respectively, promoted and impeded astrocyte differentiation in the developing brain. Our findings suggest that hypoxia contributes to the appropriate scheduling of mgNPC fate determination.

Original languageEnglish
Pages (from-to)561-569
Number of pages9
JournalStem Cells
Volume30
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1
Externally publishedYes

Keywords

  • Astrocyte differentiation
  • DNA methylation
  • Epigenetic gene regulation
  • Neural precursor cell
  • Notch signaling
  • Oxygen concentration

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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