Model demonstrating role of Nrf2 in HSPCs. (A) In Nrf2^+/+ BM, normal levels of Nrf2 are associated with low levels of ROS in HSPCs and intact cytokine signaling. (B) In Nrf2^−/− BM, basal levels ROS are not increased in HSPCs, but HSPC survival is decreased due to reduced cytokine signaling levels. Nrf2^−/− stem/progenitor cells show increased sensitivity to induced ROS. (C) G-CSF induces ROS in both Nrf2^+/+ and Nrf2^−/− HSPCs. Although Nrf2 loss is associated with increased sensitivity to ROS, G-CSF is able to restore HSPC survival despite an increase in ROS.