Selp is the top AS candidate and contributes to HSC functional decline. (A) SELP protein expression level across different hematopoietic stem and progenitors (HSPCs) in young (gray) and aged (red) mice. Panel shows FCs of aged (n = 3 mice) samples normalized to their young (n = 3 mice) counterparts. Dots show biological replicates, while the bars represent the mean values for the given population. Flow cytometry plot for SELP expression in young and aged LT-HSCs population in the 3 biological replicates. (B) Selp^high LT-HSCs display a myeloid bias. The upper panel shows the experimental approach for competitive transplantation. SELP^low (blue) and SELP^high (orange) LT-HSCs were purified from aged mice and competitively transplanted (n = 6-7 mice for each group). Overall engraftment (white blood cells [WBC]) and T cells levels were similar comparing both groups, whereas myeloid (My) and T-cell levels indicate that transplanted LT-HSC SELP^high have myeloid bias. (C) SELP overexpression (OE) recipients show impairment of erythroid differentiation. The upper panel shows the experimental approach for competitive transplantation of SELP overexpression and empty vector (EV) HSCs. Lower panel displays peripheral blood (PB) output of the GFP⁺ (transduced cells) of both groups (n = 3 per group). Within the GFP⁺ population, the Ter-119⁺ population is significantly reduced. For all panels, mean ± standard deviation is shown. ns, nonsignificant; ****P < .0001; n indicates biological replicates.