| First Author | Xu H | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 17 | Pages | 3557-66 |
| PubMed ID | 19713466 | Mgi Jnum | J:153838 |
| Mgi Id | MGI:4366395 | Doi | 10.1182/blood-2009-02-205815 |
| Citation | Xu H, et al. (2009) Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. Blood 114(17):3557-66 |
| abstractText | Hematopoietic stem cell (HSC) engraftment is a multistep process involving HSC homing to bone marrow, self-renewal, proliferation, and differentiation to mature blood cells. Here, we show that loss of p190-B RhoGTPase activating protein, a negative regulator of Rho GTPases, results in enhanced long-term engraftment during serial transplantation. This effect is associated with maintenance of functional HSC-enriched cells. Furthermore, loss of p190-B led to marked improvement of HSC in vivo repopulation capacity during ex vivo culture without altering proliferation and multilineage differentiation of HSC and progeny. Transcriptional analysis revealed that p190-B deficiency represses the up-regulation of p16(Ink4a) in HSCs in primary and secondary transplantation recipients, providing a possible mechanism of p190-B-mediated HSC functions. Our study defines p190-B as a critical transducer element of HSC self-renewal activity and long-term engraftment, thus suggesting that p190-B is a target for HSC-based therapies requiring maintenance of engraftment phenotype. |
