1. Erythropoietin receptor signaling regulates both erythropoiesis and megakaryopoiesis in vivo
- Author
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Josef T. Prchal, Gerald J. Spangrude, George Chen, L. Jeanne Pierce, Ko Tung Chang, and Xiaosong Huang
- Subjects
Erythrocytes ,Time Factors ,Genotype ,Mice, Transgenic ,beta-Globins ,Biology ,Article ,Thrombopoiesis ,Mice ,hemic and lymphatic diseases ,medicine ,Receptors, Erythropoietin ,Animals ,Humans ,Protein Isoforms ,Erythropoiesis ,Gene Knock-In Techniques ,Progenitor cell ,Molecular Biology ,Erythroid Precursor Cells ,Cells, Cultured ,Megakaryopoiesis ,Bone Marrow Transplantation ,Megakaryocyte Progenitor Cells ,Graft Survival ,Cell Biology ,Hematology ,Molecular biology ,Erythropoietin receptor ,Cell biology ,Mice, Inbred C57BL ,Haematopoiesis ,medicine.anatomical_structure ,Phenotype ,Erythropoietin ,Molecular Medicine ,Cytokines ,Bone marrow ,medicine.drug ,Signal Transduction - Abstract
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.
- Published
- 2009