| First Author | Fernando RN | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 14 | Pages | 5837-42 |
| PubMed ID | 21436033 | Mgi Jnum | J:171217 |
| Mgi Id | MGI:4949006 | Doi | 10.1073/pnas.1014993108 |
| Citation | Fernando RN, et al. (2011) Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells. Proc Natl Acad Sci U S A 108(14):5837-42 |
| abstractText | Adult neural stem cell proliferation is dynamic and has the potential for massive self-renewal yet undergoes limited cell division in vivo. Here, we report an epigenetic mechanism regulating proliferation and self-renewal. The recruitment of the PI3K-related kinase signaling pathway and histone H2AX phosphorylation following GABA(A) receptor activation limits subventricular zone proliferation. As a result, NSC self-renewal and niche size is dynamic and can be directly modulated in both directions pharmacologically or by genetically targeting H2AX activation. Surprisingly, changes in proliferation have long-lasting consequences on stem cell numbers, niche size, and neuronal output. These results establish a mechanism that continuously limits proliferation and demonstrates its impact on adult neurogenesis. Such homeostatic suppression of NSC proliferation may contribute to the limited self-repair capacity of the damaged brain. |
