Author response: Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

Blomfield, Isabelle Maria; Rocamonde, Brenda; Masdeu, M.; Mulugeta, Eskeatnaf; Vaga, Stefania; Berg, Debbie Lc van den; Huillard, Emmanuelle; Guillemot, François; Urbán, Noelia

doi:10.7554/elife.48561.028

Cited by 2 publications

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Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

Harris

Rigo

Stiehl

et al. 2020

Preprint

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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.

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Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

Harris

Rigo

Stiehl

et al. 2020

Preprint

Self Cite

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The significance of gene expression dynamics in neural stem cell regulation

Kageyama

Ochi

Sueda

et al. 2020

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Neural stem cells (NSCs) actively proliferate and generate neurons and glial cells (active state) in the embryonic brain, whereas they are mostly dormant (quiescent state) in the adult brain. The expression dynamics of Hes1 are different between active and quiescent NSCs. In active NSCs, Hes1 expression oscillates and periodically represses the expression of proneural genes such as Ascl1 , thereby driving their oscillations. By contrast, in quiescent NSCs, Hes1 oscillations maintain expression at higher levels even at trough phases (thus continuous), thereby continuously suppressing proneural gene expression. High levels of Hes1 expression and the resultant suppression of Ascl1 promote the quiescent state of NSCs, whereas oscillatory Hes1 expression and the resultant oscillatory Ascl1 expression regulate their active state. Furthermore, in other developmental contexts, high, continuous Hes1 expression induces astrocyte differentiation or the formation of boundaries, which function as signaling centers. Thus, the expression dynamics of Hes1 are a key regulatory mechanism generating and maintaining various cell types in the nervous system.

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Author response: Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

Cited by 2 publications

References 0 publications

Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

Progressive changes in hippocampal stem cell properties ensure lifelong neurogenesis

The significance of gene expression dynamics in neural stem cell regulation

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