Model for EPO-induced endogenous recovery of the erythron after sublethal radiation stress centered on the expansion, maturation, and migration of bone marrow erythroid progenitors. (A) Sublethal (4 Gy) irradiation causes the near-total loss of erythroid progenitors and precursors in bone marrow, peripheral blood, and spleen leading to the gradual onset of anemia. (B) This anemia induces EPO, which causes the specific, rapid expansion of late-stage erythroid progenitors (d3 BFU-E and CFU-E) in the bone marrow. (C) d3 BFU-E and CFU-E mature into erythroblast precursors and circulating red cells to provide a rapid, short-term erythroid response to acute radiation stress. (D) Simultaneously, early and late-stage erythroid progenitors transiently circulate into the bloodstream. (E) The spleen is subsequently seeded by circulating erythroid progenitors and undergoes robust erythroid reconstitution to augment recovery of the erythron.