| First Author | Miyamoto K | Year | 2007 |
| Journal | Cell Stem Cell | Volume | 1 |
| Issue | 1 | Pages | 101-12 |
| PubMed ID | 18371339 | Mgi Jnum | J:142870 |
| Mgi Id | MGI:3822292 | Doi | 10.1016/j.stem.2007.02.001 |
| Citation | Miyamoto K, et al. (2007) Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1(1):101-12 |
| abstractText | Hematopoietic stem cells (HSCs) are maintained in an undifferentiated quiescent state within a bone marrow niche. Here we show that Foxo3a, a forkhead transcription factor that acts downstream of the PTEN/PI3K/Akt pathway, is critical for HSC self-renewal. We generated gene-targeted Foxo3a(-/-) mice and showed that, although the proliferation and differentiation of Foxo3a(-/-) hematopoietic progenitors were normal, the number of colony-forming cells present in long-term cocultures of Foxo3a(-/-) bone marrow cells and stromal cells was reduced. The ability of Foxo3a(-/-) HSCs to support long-term reconstitution of hematopoiesis in a competitive transplantation assay was also impaired. Foxo3a(-/-) HSCs also showed increased phosphorylation of p38MAPK, an elevation of ROS, defective maintenance of quiescence, and heightened sensitivity to cell-cycle-specific myelotoxic injury. Finally, HSC frequencies were significantly decreased in aged Foxo3a(-/-) mice compared to the littermate controls. Our results demonstrate that Foxo3a plays a pivotal role in maintaining the HSC pool. |
