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Nature. 2016 Jun 16;534(7607):335-40. doi: 10.1038/nature18282.

Stem cell function and stress response are controlled by protein synthesis.

Author information

1
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
2
Department of Biology &Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
3
University of Cambridge, CR-UK, Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.

Abstract

Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.

PMID:
27306184
PMCID:
PMC5040503
DOI:
10.1038/nature18282
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interest.

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