Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence.

Otsuki, L; Brand, A H · Science · 2018

basic_science · Level V

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Abstract

Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in <i>Drosophila</i> are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G<sub>0</sub> In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G<sub>2</sub> or G<sub>0</sub> G<sub>2</sub>-G<sub>0</sub> heterogeneity directs NSC behavior: G<sub>2</sub> qNSCs reactivate before G<sub>0</sub> qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G<sub>2</sub> NSCs to enter quiescence by promoting degradation of Cdc25<sup>String</sup> and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences <i>trbl</i> transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.

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