| First Author | Zelentsova-Levytskyi K | Year | 2017 |
| Journal | Front Mol Neurosci | Volume | 10 |
| Pages | 124 | PubMed ID | 28512399 |
| Mgi Jnum | J:312248 | Mgi Id | MGI:6783587 |
| Doi | 10.3389/fnmol.2017.00124 | Citation | Zelentsova-Levytskyi K, et al. (2017) Protein S Negatively Regulates Neural Stem Cell Self-Renewal through Bmi-1 Signaling. Front Mol Neurosci 10:124 |
| abstractText | Revealing the molecular mechanisms underlying neural stem cell self-renewal is a major goal toward understanding adult brain homeostasis. The self-renewing potential of neural stem and progenitor cells (NSPCs) must be tightly regulated to maintain brain homeostasis. We recently reported the expression of Protein S (PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC quiescence and neuronal differentiation. Here, we investigate the effect of PROS1 on NSPC self-renewal and show that genetic ablation of Pros1 in neural progenitors increased NSPC self-renewal by 50%. Mechanistically, we identified the upregulation of the polycomb complex protein Bmi-1 and repression of its downstream effectors p16(Ink4a) and p19(Arf) to promote NSPC self-renewal in Pros1-ablated cells. Rescuing Pros1 expression restores normal levels of Bmi-1 signaling, and reverts the proliferation and enhanced self-renewal phenotypes observed in Pros1-deleted cells. Our study identifies PROS1 as a novel negative regulator of NSPC self-renewal. We conclude PROS1 is instructive for NSPC differentiation by negatively regulating Bmi-1 signaling in adult and embryonic neural stem cells. |
