ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)300-314.e6
JournalCell Stem Cell
Issue number2
Publication statusPublished - 4 Feb 2021

External IDs

PubMed 33275875
ORCID /0000-0002-5304-4061/work/142238785



  • adult neurogenesis, adult stem cells, physical activity, quiescent neural stem cells, reactive oxygen species, stem cell heterogeneity

Library keywords