| First Author | Ghiaur G | Year | 2008 |
| Journal | Blood | Volume | 111 |
| Issue | 7 | Pages | 3313-21 |
| PubMed ID | 18083846 | Mgi Jnum | J:133470 |
| Mgi Id | MGI:3778605 | Doi | 10.1182/blood-2007-08-110114 |
| Citation | Ghiaur G, et al. (2008) Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells. Blood 111(7):3313-21 |
| abstractText | Definitive hematopoietic stem and progenitor cells (HSCs/Ps) originating from the yolk sac and/or para-aorta-splanchno-pleura/aorta-gonad-mesonephros are hypothesized to colonize the fetal liver, but mechanisms involved are poorly defined. The Rac subfamily of Rho GTPases has been shown to play essential roles in HSC/P localization to the bone marrow following transplantation. Here, we study the role of Rac1 in HSC/P migration during ontogeny and seeding of fetal liver. Using a triple-transgenic approach, we have deleted Rac1 in HSCs/Ps during very early embryonic development. Without Rac1, there was a decrease in circulating HSCs/Ps in the blood of embryonic day (E) 10.5 embryos, while yolk sac definitive hematopoiesis was quantitatively normal. Intraembryonic hematopoiesis was significantly impaired in Rac1-deficient embryos, culminating with absence of intra-aortic clusters and fetal liver hematopoiesis. At E10.5, Rac1-deficient HSCs/Ps displayed decreased transwell migration and impaired inter-action with the microenvironment in migration-dependent assays. These data suggest that Rac1 plays an important role in HSC/P migration during embryonic development and is essential for the emergence of intraembryonic hematopoiesis. |
