RT Journal Article
SR Electronic
T1 Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.12.987107
DO 10.1101/2020.03.12.987107
A1 Harris, Lachlan
A1 Rigo, Piero
A1 Stiehl, Thomas
A1 Gaber, Zachary
A1 Austin, Sophie H. L.
A1 del Mar Masdeu, Maria
A1 Edwards, Amelia
A1 Urbán, Noelia
A1 Marciniak-Czochra, Anna
A1 Guillemot, François
YR 2020
UL http://biorxiv.org/content/early/2020/03/12/2020.03.12.987107.abstract
AB Neural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilise during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this reduction in stem cell depletion rate is the result of multiple coordinated changes in stem cell behaviour. In particular, while active neural stem cells divide only once or twice before differentiating rapidly in juveniles, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomic, mathematical modelling 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 progressive changes in stem cell behaviour result from reduced expression of the pro-activation protein ASCL1 due to increased post-translational degradation. These mechanisms help reconcile current contradictory models of hippocampal NSC dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species including humans.