HSCs: stressing out over ROS.

摘要

In this issue of Blood, Yahata and colleagues demonstrate that reactive oxygen species (ROS)-induced DNA damage impairs the self-renewal capacity of human HSCs, and that oxidative DNA damage repair is less efficient in quiescent stem cells than in progenitor cells. HSCs are a rare population of pluripotent cells that can self-renew and produce various types of cells of the blood lineage. Under steady physiologic conditions, the most primitive HSCs are 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. In response to stress or stimulation, the HSCs can move out of the BM niche, entering cell cycle and undergoing division (see figure panel A). In addition, the cycling HSCs may return to the BM niche and regain their quiescent state. Disruption of HSC quiescence prematurely exhausts the HSC pool and causes hematologic failure under various stresses, such as oxidative, replica-tive, and metabolic, and DNA damage.