Submitted April 11, 2006
Accepted January 24, 2007
BMP4, SCF and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors
John M. Perry, Omid F Harandi, and Robert F. Paulson*
Huck Institutes of the Life Sciences Cell & Developmental Biology Option, Pennsylvania State Univ., University Park, PA, United States
The Graduate Program in Genetics, Pennsylvania State Univ., University Park, PA, United States
The Department of Veterinary & Biomedical Sciences, Pennsylvania State Univ., University Park, PA, United States
* Corresponding author; email: rfp5{at}psu.edu.
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 Sickle cell anemia and 
-thalassemia patients. 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.
