HSC maintenance under oxidative stress. (A) Under steady-state conditions, HSCs are maintained in a quiescent state and reside in the BM niche where they preserve the capacity to self-renew and to continue to produce all types of blood cells throughout a prolonged lifespan. (B) ROS generated by replicative stress during serial transplantation can induce DNA damage and drive HSCs into cell division, which could cause progressive loss of HSC functions. After successful repair of the oxidative DNA damage, HSCs can return to quiescent state.