BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors
- 6 February 2007
- journal article
- Published by American Society of Hematology in Blood
- Vol. 109 (10), 4494-4502
- https://doi.org/10.1182/blood-2006-04-016154
Abstract
The erythroid response to acute anemia relies on the rapid expansion in the spleen of a specialized population of erythroid progenitors termed stress BFU-E. This expansion requires BMP4/Madh5-dependent signaling in vivo; however, in vitro, BMP4 alone cannot recapitulate the expansion of stress BFU-E observed in vivo, which suggests that other signals are required. In this report we show that mutation of the Kit receptor results in a severe defect in the expansion of stress BFU-E, indicating a role for the Kit/SCF signaling pathway in stress erythropoiesis. In vitro analysis showed that BMP4 and SCF are necessary for the expansion of stress BFU-E, but only when spleen cells were cultured in BMP4 + SCF at low-oxygen concentrations did we recapitulate the expansion of stress BFU-E observed in vivo. Culturing spleen cells in BMP4, SCF under hypoxic conditions resulted in the preferential expansion of erythroid progenitors characterized by the expression of Kit, CD71, and TER119. This expression pattern is also seen in stress erythroid progenitors isolated from patients with sickle cell anemia and patients with β-thalassemia. Taken together these data demonstrate that SCF and hypoxia synergize with BMP4 to promote the expansion and differentiation of stress BFU-E during the recovery from acute anemia.Keywords
This publication has 42 references indexed in Scilit:
- Core erythropoietin receptor signals for late erythroblast developmentBlood, 2006
- Resistance to Friend Virus-Induced Erythroleukemia in W / W
v
Mice Is Caused by a Spleen-Specific Defect Which Results in a Severe Reduction in Target Cells and a Lack of Sf-Stk ExpressionJournal of Virology, 2005
- BMP4 and Madh5 regulate the erythroid response to acute anemiaBlood, 2005
- Human CD34+ and CD34+CD38− hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cellsExperimental Hematology, 2004
- Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry–based novel culture systemBlood, 2003
- Mutations in the VHL gene in sporadic apparently congenital polycythemiaBlood, 2003
- Disruption of oxygen homeostasis underlies congenital Chuvash polycythemiaNature Genetics, 2002
- Thrombocytopenic c-mpl−/− mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the responseBlood, 2001
- Ineffective erythropoiesis in β-thalassemia major is due to apoptosis at the polychromatophilic normoblast stageExperimental Hematology, 2000
- Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1αGenes & Development, 1998