HOXA10 determines the fate of hematopoietic stem and progenitor cells in a concentration-dependent manner. This model explains how distinct hematopoietic cell fates are regulated by HOXA10. Intermediate levels of HOXA10 stimulate proliferation of repopulating HSCs and lead to a 15-fold increase in their repopulation capacity, whereas high concentrations of HOXA10 maintain or have a slight reduction in repopulation ability without affecting viability of HSCs. Low/intermediate concentration of HOXA10 increases the output of CFU-GM progenitors, macrophages, and neutrophils, whereas high concentrations lead to accumulation of GMPs. High concentrations of HOXA10 lead to a block in erythroid and megakaryocytic development and accumulation of MEPs. Similarly, high concentrations of HOXA10 lead to a reduction in T-cell development in vivo without affecting B-cell development. The ↑ indicates increase; ↓, decrease; ×, block.