Complementary and Independent Functionfor Hoxb4 and Bmil in HSC Activity

摘要

Determinants regulating short- and long-term repopulating hematopoietic stem cell (STR-HSC and LTR-HSC) self-renewalremain largely uncharacterized. To gain further insights into HSC self-renewal, we investigated possible genetic interactionsbetween two well-recognized regulators of this process: Broil and Hoxb4. Using complementation and overexpression strate-gies in mouse HSCs, we document that Bind is not required for the in vivo expansion of fetal HSCs but is essential for thelong-term maintenance of adult HSCs. Importantly, we show that lloxb4 overexpression induces an expansion of Bmi 1 STR-HSCs leading to a rescue of their repopulation defect. In contrast to Hoxb4, we also show that Bmi 1 fails to induce HSCexpansion ex vivo. Consistent with these results, we report high levels of Angptl3 and Cbx7 in Hoxb4- and Bmil-transducedcells, respectively. Together, these results support the emerging concept that fate and sustainability of this fate are two criti-cal components of self-renewal in adult stem cells such as HSCs.