Cellular redox states regulate the balance between stem cell maintenance and activation. Increased levels of intracellular reactive oxygen species (ROS) are linked to proliferation and lineage specification. In contrast to this general principle, we here show that in the hippocampus of adult mice, quiescent neural precursor cells (NPCs) maintain the highest ROS levels (hiROS). Classifying NPCs on the basis of cellular ROS content identified distinct functional states. Shifts in ROS content primed cells for a subsequent state transition, with lower ROS content marking proliferative activity and differentiation. Physical activity, a physiological activator of adult hippocampal neurogenesis, recruited hiROS NPCs into proliferation via a transient Nox2-dependent ROS surge. In the absence of Nox2, baseline neurogenesis was unaffected, but the activity-induced increase in proliferation disappeared. These results provide a metabolic classification of NPC functional states and describe a mechanism linking the modulation of cellular ROS by behavioral cues to the activation of adult NPCs.

细胞氧化还原状态调节干细胞维持和激活之间的平衡。细胞内活性氧（ROS）水平的提高与增殖和谱系规格有关。与此一般原则相反，我们在这里显示在成年小鼠海马中，静止的神经前体细胞（NPC）保持最高的ROS水平（hiROS）。根据细胞ROS含量对NPC进行分类可确定不同的功能状态。ROS含量的变化引发了细胞的后续状态转换，其中较低的ROS含量标志着增殖活性和分化。体力活动是成人海马神经发生的生理激活剂，它通过短暂的Nox2依赖性ROS激增使hiROS NPC进入增殖状态。在没有Nox2的情况下，基线神经发生不受影响，但是活性诱导的增殖增加消失了。这些结果提供了NPC功能状态的代谢分类，并描述了通过行为线索将细胞ROS的调节与成人NPC的激活联系起来的机制。