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Stem cell function and stress response are controlled by protein synthesis

Author

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  • Sandra Blanco

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Roberto Bandiera

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Martyna Popis

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Shobbir Hussain

    (University of Bath)

  • Patrick Lombard

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Jelena Aleksic

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Abdulrahim Sajini

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Hinal Tanna

    (University of Cambridge, CR-UK, Cambridge Institute, Li Ka Shing Centre)

  • Rosana Cortés-Garrido

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Nikoletta Gkatza

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Sabine Dietmann

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

  • Michaela Frye

    (Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge)

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.

Suggested Citation

  • Sandra Blanco & Roberto Bandiera & Martyna Popis & Shobbir Hussain & Patrick Lombard & Jelena Aleksic & Abdulrahim Sajini & Hinal Tanna & Rosana Cortés-Garrido & Nikoletta Gkatza & Sabine Dietmann & M, 2016. "Stem cell function and stress response are controlled by protein synthesis," Nature, Nature, vol. 534(7607), pages 335-340, June.
    • Handle: RePEc:nat:nature:v:534:y:2016:i:7607:d:10.1038_nature18282
    DOI: 10.1038/nature18282
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    Cited by:

    1. Joana Silva & Ferhat Alkan & Sofia Ramalho & Goda Snieckute & Stefan Prekovic & Ana Krotenberg Garcia & Santiago Hernández-Pérez & Rob Kammen & Danielle Barnum & Liesbeth Hoekman & Maarten Altelaar & , 2022. "Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Pierre Sabatier & Christian M. Beusch & Amir A. Saei & Mike Aoun & Noah Moruzzi & Ana Coelho & Niels Leijten & Magnus Nordenskjöld & Patrick Micke & Diana Maltseva & Alexander G. Tonevitsky & Vincent , 2021. "An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. António Rua & Fátima Cardoso, 2023. "Gone with the wind: A structural decomposition of carbon emissions," Working Papers w202312, Banco de Portugal, Economics and Research Department.
    4. Jianheng Liu & Tao Huang & Wanying Chen & Chenhui Ding & Tianxuan Zhao & Xueni Zhao & Bing Cai & Yusen Zhang & Song Li & Ling Zhang & Maoguang Xue & Xiuju He & Wanzhong Ge & Canquan Zhou & Yanwen Xu &, 2022. "Developmental mRNA m5C landscape and regulatory innovations of massive m5C modification of maternal mRNAs in animals," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Kristin A. Fluke & Ryan T. Fuchs & Yueh-Lin Tsai & Victoria Talbott & Liam Elkins & Hallie P. Febvre & Nan Dai & Eric J. Wolf & Brett W. Burkhart & Jackson Schiltz & G. Brett Robb & Ivan R. Corrêa & T, 2024. "The extensive m5C epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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