The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Stem cell function and stress response are controlled by protein synthesis
Open accessAbstract
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. The protein translation rate is low in tissue stem cells and tumour-initiating cells, and genetically preventing cytosine-5 methylation on transfer RNA in skin tumours is shown to favour the maintenance of a state of translational inhibition in mice, with tumour-initiating cells in this state becoming more sensitive to cytotoxic stress. The relationship between protein synthesis regulation and stem cell function is unclear. Michaela Frye and colleagues show here that mouse skin stem cells and tumour-initiating cells synthesize less protein than their more differentiated daughters. The genetic prevention of cytosine-5 methylation on transfer RNA favours the maintenance of a state of translational inhibition in mice, with stem cells and tumour-initiating cells in this state becoming more sensitive to cytotoxic stress, indicating that both tissue or tumour regeneration require the release of this inhibition.
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Metadata
- Authors
- Blanco, S., Bandiera, R., Popis, M., Hussain, S., Lombard, P., Aleksic, J., Sajini, A., Tanna, H., Cortés-Garrido, R., Gkatza, N., Dietmann, S., & Frye, M.
- Venue
- Nature
- Published
- 2016-06
- Volume
- 534
- Issue
- 7607
- Pages
- 335-340
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2430983120
- Cited by
- 466
- References
- 59
- FWCI
- 15.05
- Type
- journal article
- Language
- en
- Open access
- green
- Licence
- www.springer.com/tdm (tdm)
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- Blanco, S., Bandiera, R., Popis, M., Hussain, S., Lombard, P., Aleksic, J., Sajini, A., Tanna, H., Cortés-Garrido, R., Gkatza, N., Dietmann, S., & Frye, M. (2016). Stem cell function and stress response are controlled by protein synthesis. Nature. https://doi.org/10.1038/nature18282
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