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

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Science  06 Apr 2018:
Vol. 360, Issue 6384, pp. 99-102
DOI: 10.1126/science.aan8795

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Staging quiescent cells

Tissue-specific stem cells either divide or wait in a quiescent state until needed by the body. Quiescent stem cells have been thought to reside in the G0 stage before activating to reenter the cell cycle. However, Otsuki and Brand now show that most quiescent stem cells in the Drosophila brain are arrested in G2. Cells in the two phases display differences; for example, G2 stem cells awaken more quickly than G0 stem cells, with the conserved pseudokinase Tribbles playing a regulatory role. Elucidating the different pathways and mechanisms underlying quiescence could help to inform regenerative drug design.

Science, this issue p. 99

Abstract

Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in Drosophila are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G0. In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G2 or G0. G2-G0 heterogeneity directs NSC behavior: G2 qNSCs reactivate before G0 qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G2 NSCs to enter quiescence by promoting degradation of Cdc25String and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences trbl transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.

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