期刊
STEM CELL REPORTS
卷 10, 期 6, 页码 1705-1720出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2018.04.024
关键词
-
资金
- Children's Hospital of Colorado Research Foundation
- NIH/National Institute of Neurological Disorders and Stroke [R01 NS098273]
Neural stem and precursor cell (NSPC) proliferation in the rodent adult hippocampus is essential to maintain stem cell populations and produce new neurons. Retinoic acid (RA) signaling is implicated in regulation of adult hippocampal neurogenesis, but its exact role in control of NSPC behavior has not been examined. We show RA signaling in all hippocampal NSPC subtypes and that inhibition of RA synthesis or signaling significantly decreases NSPC proliferation via abrogation of cell-cycle kinetics and cell-cycle regulators. RA signaling controls NSPC proliferation through hypoxia inducible factor-1 alpha (HIF1 alpha), where stabilization of HIF1 alpha concurrent with disruption of RA signaling can prevent NSPC defects. These studies demonstrate a cell-autonomous role for RA signaling in hippocampal NSPCs that substantially broadens RA's function beyond its well-described role in neuronal differentiation.
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