Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population
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Lachlan Harris Piero Rigo Thomas Stiehl Zachary Gaber Sophie Austin Maria Del Mar Masdeu Camara Amelia Edwards Noelia Urbán Anna Marciniak-Czochra Francois GuillemotAbstract
Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilize during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this stabilization of stem cell numbers in young adults is the result of coordinated changes in stem cell behavior. Although proliferating neural stem cells in juveniles differentiate rapidly, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomics, modeling, and label retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These changes in stem cell behavior result from a progressive reduction in expression of the pro-activation protein ASCL1 because of increased post-translational degradation. These cellular mechanisms help reconcile current contradictory models of hippocampal neural stem cell (NSC) dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species, including humans.
Journal details
Journal Cell Stem Cell
Volume 28
Issue number 5
Pages 863-876.e6
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.stem.2021.01.003
Figshare View on figshare
Europe PubMed Central 33581058
Pubmed 33581058