| First Author | Sorimachi Y | Year | 2021 |
| Journal | J Biol Chem | Volume | 296 |
| Pages | 100563 | PubMed ID | 33745970 |
| Mgi Jnum | J:313272 | Mgi Id | MGI:6695577 |
| Doi | 10.1016/j.jbc.2021.100563 | Citation | Sorimachi Y, et al. (2021) p38alpha plays differential roles in hematopoietic stem cell activity dependent on aging contexts. J Biol Chem :100563 |
| abstractText | Hematopoietic stem cells (HSCs) and their progeny sustain lifetime hematopoiesis. Aging alters HSC function, number, and composition and increases risk of hematological malignancies, but how these changes occur in HSCs remains unclear. Signaling via p38MAPK has been proposed as a candidate mechanism underlying induction of HSC aging. Here, using genetic models of both chronological and premature aging, we describe a multimodal role for p38alpha, the major p38MAPK isozyme in hematopoiesis, in HSC aging. We report that p38alpha regulates differentiation bias and sustains transplantation capacity of HSCs in the early phase of chronological aging. However, p38alpha decreased HSC transplantation capacity in the late progression phase of chronological aging. Furthermore, co-deletion of p38alpha in mice deficient in Ataxia-telangiectasia mutated (Atm), a model of premature aging, exacerbated aging-related HSC phenotypes seen in Atm single mutant mice. Overall, these studies provide new insight into multiple functions of p38MAPK, which both promotes and suppresses HSC aging context-dependently. |
