期刊
STEM CELLS
卷 30, 期 3, 页码 561-569出版社
WILEY
DOI: 10.1002/stem.1019
关键词
Neural precursor cell; Astrocyte differentiation; DNA methylation; Epigenetic gene regulation; Notch signaling; Oxygen concentration
资金
- Ministry of Health, Labor and Welfare, Japan
- Innovative Area: Neural Diversity and Neocortical Organization
- Program of Innovative Cell Biology by Innovative Technology
- NAIST Global COE from the Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [23123515] Funding Source: KAKEN
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 1 alpha (HIF1 alpha) plays a critical role in astrocytic gene demethylation in mgNPCs by cooperating with the Notch signaling pathway. Expression of constitutively active HIF1 alpha 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. STEM CELLS 2012;30:561-569
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