STAT5-induced IRS2 engages IGF1R signaling to promote sCFU-E growth. (A) Epo-induced expression of candidate STAT5 target genes in sorted BFU-E, sCFU-E, and CFU-E cells by qPCR. (B) Phlebotomy induces IRS2 expression in sCFU-E cells. Statistically significant differences indicated on top of each bar are comparison with BFU-E cells, whereas significant differences between nonphlebotomized and phlebotomized (phleb.) conditions are specified. (C) Epo-induced IRS2 expression is defective in sCFU-E and CFU-E cells of EpoR(core) mice. (D) Y343 rescues Epo-induced IRS2 expression in EpoR(core+Y343) sCFU-E and CFU-E cells. (E) IGF1 increases sCFU-E colonies in mice expressing wild-type (WT) but not EpoR(core). (F) IGF1 injection accelerates RBC recovery after phlebotomy. (G) Exogenous expression of IRS2 increases the growth of sCFU-E cells and the number of Ter119⁺ progenies generated in bone marrow cells from EpoR(core). GFP⁺ cells were gated for analyses and normalized to vector controls. Veh., vehicle control. ∗P < .05; ∗∗P < .01, 1-way or 2-way ANOVA.