Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence.
Science (New York, N.Y.)
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Otsuki, L., & Brand, A. (2018). Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence.. Science (New York, N.Y.), 360 (6384), 99-102. https://doi.org/10.1126/science.aan8795
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 signalling 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 subsequently maintains quiescence by inhibiting Akt activation. Insulin signalling 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.
Animals, Drosophila melanogaster, Insulin, Protein-Serine-Threonine Kinases, Cell Cycle Proteins, Drosophila Proteins, Regeneration, Signal Transduction, Cell Cycle, Time Factors, Proto-Oncogene Proteins c-akt, Protein Tyrosine Phosphatases, Neurogenesis, Neural Stem Cells, Proteolysis
This work was funded by the Royal Society Darwin Trust Research Professorship, Wellcome Trust Senior Investigator Award 103792 and Wellcome Trust Programme grant 092545 to A.H.B., and Wellcome Trust PhD Studentship 097423 to L.O. A.H.B acknowledges core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492).
Wellcome Trust (092545/Z/10/Z)
WELLCOME TRUST (103792/Z/14/Z)
Royal Society (RP150061)
Wellcome Trust (097423/Z/11/Z)
Wellcome Trust (092096/Z/10/Z)
Cancer Research UK (A14492)
External DOI: https://doi.org/10.1126/science.aan8795
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276751