ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence.
Date
2021-02-04ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
adult neurogenesis
adult stem cells
physical activity
quiescent neural stem cells
reactive oxygen species
stem cell heterogeneity
Animals
Cell Differentiation
Cell Proliferation
Hippocampus
Mice
Neural Stem Cells
Neurogenesis
Reactive Oxygen Species
Research team
Post-transl modification
Language
eng
Date accepted
2020-10-29
License start date
2021-02-04
Citation
Cell Stem Cell, 2021, 28 (2), pp. 300 - 314.e6
Publisher
CELL PRESS