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- W2108687101 abstract "HIF-1α is a hypoxia-inducible protein that regulates many cell and molecular processes, including those involved in angiogenesis and stem cell maintenance. Prior studies demonstrated constitutive HIF-1α stabilization in neural stem cells (NSCs) of the adult mouse SVZ, but its role there has not been elucidated. Here, we tested the hypothesis that HIF-1α plays an essential role in the maintenance of adult NSCs and stabilization of the SVZ vascular niche using conditional, tamoxifen-inducible Hif1a knock-out mice. We generated nestin-CreER T2 /R26R-YFP/ Hif1a fl/fl triple transgenic mice, to enable tamoxifen-inducible Hif1a gene inactivation in nestin-expressing NSCs within the adult SVZ. Hif1a gene deletion resulted in a significant loss of YFP + NSCs within the SVZ by 45 d post recombination, which was preceded by significant regression of the SVZ vasculature at 14 d, and concomitant decrease of VEGF expression by NSCs. Loss of YFP + NSCs following Hif1a gene inactivation in vivo was likely an indirect consequence of vascular regression, since YFP + neurosphere formation over serial passage was unaffected. These results identify NSC-encoded HIF-1α as an essential factor in the maintenance of the adult SVZ, and demonstrate that NSCs within the SVZ maintain the integrity of their vascular niche through HIF-1α-mediated signaling mechanisms." @default.
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- W2108687101 date "2014-12-10" @default.
- W2108687101 modified "2023-09-26" @default.
- W2108687101 title "Hypoxia Inducible Factor-1α (HIF-1α) Is Required for Neural Stem Cell Maintenance and Vascular Stability in the Adult Mouse SVZ" @default.
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- W2108687101 doi "https://doi.org/10.1523/jneurosci.4590-13.2014" @default.
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