Are bone marrow and splenic erythroid progenitors distinct?
Are EpoR-H signals unique to adult splenic progenitors? In other words, are adult splenic erythroid progenitors distinct from adult bone marrow erythroid progenitors? Apparently not, since ex vivo cultures of EpoR-HM adult bone marrow–derived erythroid progenitors also exhibited defects in Epo-induced proliferation and evidence of increased apoptosis — defects rescued by restoration of the Stat5 PY site (3). But these analyses are, by their nature, performed out of biological context and thus do not account for potential differences in microenvironmental regulation. The recent reexamination of flexed-tail (f) mutant mice is particularly informative in this regard (12). Like Stat5a,b–/– and EpoR-HM mice, adult f/f mice exhibit normal steady-state erythropoiesis but do not respond to acute erythropoietic stress. Mutant f/f mice have a mutation in the Madh5 gene, a functional Smad molecule downstream of bone morphogenic protein (BMP) receptor signaling (Figure 1). BMP4 is rapidly, and tra
