| First Author | Oguro H | Year | 2006 |
| Journal | J Exp Med | Volume | 203 |
| Issue | 10 | Pages | 2247-53 |
| PubMed ID | 16954369 | Mgi Jnum | J:124627 |
| Mgi Id | MGI:3722045 | Doi | 10.1084/jem.20052477 |
| Citation | Oguro H, et al. (2006) Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice. J Exp Med 203(10):2247-53 |
| abstractText | The polycomb group (PcG) protein Bmi1 plays an essential role in the self-renewal of hematopoietic and neural stem cells. Derepression of the Ink4a/Arf gene locus has been largely attributed to Bmi1-deficient phenotypes in the nervous system. However, its role in hematopoietic stem cell (HSC) self-renewal remained undetermined. In this study, we show that derepressed p16(Ink4a) and p19(Arf) in Bmi1-deficient mice were tightly associated with a loss of self-renewing HSCs. The deletion of both Ink4a and Arf genes substantially restored the self-renewal capacity of Bmi1(-/-) HSCs. Thus, Bmi1 regulates HSCs by acting as a critical failsafe against the p16(Ink4a)- and p19(Arf)-dependent premature loss of HSCs. We further identified a novel role for Bmi1 in the organization of a functional bone marrow (BM) microenvironment. The BM microenvironment in Bmi1(-/-) mice appeared severely defective in supporting hematopoiesis. The deletion of both Ink4a and Arf genes did not considerably restore the impaired BM microenvironment, leading to a sustained postnatal HSC depletion in Bmi1(-/-)Ink4a-Arf(-/-) mice. Our findings unveil a differential role of derepressed Ink4a and Arf on HSCs and their BM microenvironment in Bmi1-deficient mice. Collectively, Bmi1 regulates self-renewing HSCs in both cell-autonomous and nonautonomous manners. |
