FIG. 8.

Modeling the function of FoxO3 in hematopoietic stem versus progenitor cells. The function of FoxO3 may be distinct in hematopoietic stem cells versus progenitor cells. In hematopoietic stem cells, FoxO3 is constitutively active to promote antioxidant resistance and quiescence. In hematopoietic progenitor cells that are subject to cytokines, ROS may play an active role in the regulation of cytokine-receptor signaling. In hematopoietic progenitors, FoxO3 is suppressed while ROS are under a certain threshold, above which, FoxO3 is activated to induce apoptosis. This model provides an intrinsic ROS-mediated dynamic balance between the degree of proliferation and survival of hematopoietic progenitors. Tight regulation of ROS via FoxO3 thwarts unlimited generation of hematopoietic progenitors.