ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence.
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Embargo End Date
ICR Authors
Authors
Adusumilli, VS
Walker, TL
Overall, RW
Klatt, GM
Zeidan, SA
Zocher, S
Kirova, DG
Ntitsias, K
Fischer, TJ
Sykes, AM
Reinhardt, S
Dahl, A
Mansfeld, J
Rünker, AE
Kempermann, G
Walker, TL
Overall, RW
Klatt, GM
Zeidan, SA
Zocher, S
Kirova, DG
Ntitsias, K
Fischer, TJ
Sykes, AM
Reinhardt, S
Dahl, A
Mansfeld, J
Rünker, AE
Kempermann, G
Document Type
Journal Article
Date
2021-02-04
Date Accepted
2020-10-29
Abstract
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.
Citation
Cell Stem Cell, 2021, 28 (2), pp. 300 - 314.e6
Source Title
Cell Stem Cell
Publisher
CELL PRESS
ISSN
1934-5909
eISSN
1875-9777
1875-9777
1875-9777
Collections
Research Team
Post-transl modification