EPO-responsive progenitors are not present in the spleen until after their recovery in the bone marrow. (A) Erythroid progenitor kinetics in bone marrow and spleen 2 days after IP injection of 1000 IU/kg EPO in unirradiated mice. At steady-state, EPO-responsive progenitors are present in both bone marrow and spleen and rapidly expand in response to EPO stimulation. (B) Erythroid progenitor kinetics in bone marrow and spleen at 6 days after radiation ± IP EPO injection at 4 days post–4 Gy TBI. Late-stage erythroid progenitors expand in bone marrow but do not expand in spleen, indicating that EPO-responsive progenitors are not present in spleen during the period of rapid marrow recovery. (C) Erythroid progenitor kinetics in bone marrow and spleen at 12 days after radiation ± IP EPO injection at 10 days post–4 Gy TBI. EPO responsive progenitors are present in spleen by 10 days after radiation, consistent with delayed initiation of splenic expansion. Progenitors are normalized per femur or spleen and expressed as a percent of unirradiated control. Dotted lines represent unirradiated control levels in all graphs. Error bars represent SEM of at least 3 experiments, and 3 or more independently assayed mice were used to determine each data point. Statistical analyses were performed using a 2-tailed Student t test (*P < .05; **P < .01; ***P < .001; significantly different from mock-treated mice at matched time points).