Open AccessOxygen Levels Epigenetically Regulate Fate Switching of Neural Precursor Cells via Hypoxia‐Inducible Factor 1α‐Notch Signal Interaction in the Developing Brain
Author(s) -
Mutoh Tetsuji,
Sanosaka Tsukasa,
Ito Kei,
Nakashima Kinichi
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1019
Subject(s) - biology , notch signaling pathway , microbiology and biotechnology , astrocyte , neural stem cell , embryonic stem cell , neurogenesis , hypoxia (environmental) , hypoxia inducible factors , signal transduction , oxygen , neuroscience , gene , central nervous system , biochemistry , stem cell , chemistry , organic chemistry
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. S TEM C ELLS 2012;30:561–569