Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors.
Acute anemic stress induces a systemic response designed to increase oxygen delivery to hypoxic tissues. Increased erythropoiesis is a key component of this response. Recovery from acute anemia relies on stress erythropoiesis, which is distinct from steady-state erythropoiesis. In this study we found that the bone morphogenetic protein 4-dependent (BMP4-dependent) stress erythropoiesis pathway was required and specific for erythroid short-term radioprotection following bone marrow transplantation. BMP4 signaling promoted the development of three populations of stress erythroid progenitors, which expanded in the spleen subsequent to bone marrow transplantation in mice. These progenitors did not correspond to previously identified bone marrow steady-state progenitors. The most immature population of stress progenitors was capable of self renewal while maintaining erythropoiesis without contribution to other lineages when serially transplanted into irradiated secondary and tertiary recipients. These data suggest that during the immediate post-transplant period, the microenvironment of the spleen is altered, which allows donor bone marrow cells to adopt a stress erythropoietic fate and promotes the rapid expansion and differentiation of stress erythroid progenitors. Our results also suggest that stress erythropoiesis may be manipulated through targeting the BMP4 signaling pathway to improve survival after injury.
Center for Molecular Immunology and Infectious Disease, Pennsylvania State University, University Park, Pennsylvania, USA.
Omid F
OF
Harandi
Shailaja
S
Hedge
Dai-Chen
DC
Wu
Daniel
D
McKeone
Robert F
RF
Paulson
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D004920:Erythropoiesis; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D011836:Radiation Tolerance / Q000502:physiology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013312:Stress, Physiological
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4