| First Author | Li L | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 50 | Pages | 16713-9 |
| PubMed ID | 25505323 | Mgi Jnum | J:218841 |
| Mgi Id | MGI:5618574 | Doi | 10.1523/JNEUROSCI.4590-13.2014 |
| Citation | Li L, et al. (2014) Hypoxia inducible factor-1alpha (HIF-1alpha) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ. J Neurosci 34(50):16713-9 |
| abstractText | HIF-1alpha 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-1alpha 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-1alpha 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-1alpha 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-1alpha-mediated signaling mechanisms. |
