| First Author | Kobayashi M | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 25 | Pages | 6562-71 |
| PubMed ID | 22039255 | Mgi Jnum | J:179063 |
| Mgi Id | MGI:5301028 | Doi | 10.1182/blood-2011-05-349084 |
| Citation | Kobayashi M, et al. (2011) Regulation of murine hematopoietic stem cell quiescence by Dmtf1. Blood 118(25):6562-71 |
| abstractText | The cell-cycle status of hematopoietic stem cells (HSCs) is tightly regulated, most likely to balance maintenance of stem-cell status through quiescence and expansion/differentiation of the hematopoietic system. Tumor-suppressor genes (TSGs), with their cell cycle-regulatory functions, play important roles in HSC regulation. The cyclin-D binding myb-like transcription factor 1 (Dmtf1) was recently recognized as a TSG involved in human cancers by repressing oncogenic Ras/Raf signaling. However, the role of Dmtf1 in the hematopoietic system is entirely unknown. In the present study, we demonstrate that Dmtf1 regulates HSC function under both steady-state and stress conditions. Dmtf1(-/-) mice showed increased blood cell counts in multiple parameters, and their progenitor cells had increased proliferation and accelerated cell-cycle progression. In addition, long-term HSCs from Dmtf1(-/-) mice had a higher self-renewal capacity that was clearly demonstrated in secondary recipients in serial transplantation studies. Dmtf1(-/-) BM cells showed hyper proliferation after 5-fluorouracil-induced myeloablation. Steady-state expression and Induction of CDKN1a (p21) and Arf were impaired in HSCs from Dmtf1(-/-) mice. The function of Dmtf1 was mediated by both Arf-dependent and Arf-independent pathways. Our results implicate Dmtf1 in the regulation of HSC function through novel cell cycle-regulatory mechanisms. |
