First Author | Huang X | Year | 2010 |
Journal | Blood Cells Mol Dis | Volume | 44 |
Issue | 1 | Pages | 1-6 |
PubMed ID | 19836979 | Mgi Jnum | J:233137 |
Mgi Id | MGI:5780849 | Doi | 10.1016/j.bcmd.2009.09.007 |
Citation | Huang X, et al. (2010) Erythropoietin receptor signaling regulates both erythropoiesis and megakaryopoiesis in vivo. Blood Cells Mol Dis 44(1):1-6 |
abstractText | Transgenic expression of a gain-of-function truncated mouse erythropoietin receptor gene (EpoR) leads to expansion of the HSC pool in response to human erythropoietin (Epo). We have re-examined this observation using a knock-in mouse model, wherein the mouse EpoR gene was replaced in its proper genetic locus by a single copy of either a wild-type human or a polycythemia-inducing truncated human EPOR gene. Bone marrow cells obtained from knock-in mice were transplanted together with competitor bone marrow cells in a model that allows tracking of erythroid, platelet, and leukocyte contributions by each genotype. Secondary transplants were also performed. Stem/progenitor cells were identified phenotypically and isolated for colony-forming assays to evaluate cytokine responsiveness by cells with the wild-type human or truncated human EPOR gene. Augmented Epo signaling increased erythroid repopulation post-transplant as expected, but had no effect on short-term or long-term leukocyte repopulation. However, the wild-type human EPOR knock-in mouse showed decreases in both erythroid and platelet repopulation compared to marrow cells from the mutant human EPOR knock-in mouse or normal B6 animals. These results provide evidence supporting a role for Epo signaling in megakaryopoiesis in vivo and suggest a role for Epo signaling early in hematopoietic development. |