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Stem cell function and stress response are controlled by protein synthesis

Sandra Blanco1, Roberto Bandiera1, Martyna Popis1

  • 1Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.

Nature
|June 17, 2016
PubMed

Insights

Cellular stress response pathways reduce protein synthesis in mouse skin stem cells, promoting stem cell functions and tumor growth. This inhibition must be reversed for tissue or tumor regeneration.

Area of Science:

  • Stem cell biology
  • Molecular biology
  • Cancer research

Background:

  • The interplay between protein synthesis and cellular stress response in stem cell regulation is not well understood.
  • Stem cells possess unique properties that allow them to maintain tissue homeostasis and regenerate damaged tissues.

Purpose of the Study:

  • To investigate the interaction between protein synthesis and cellular stress response pathways in controlling mouse skin stem cell function.
  • To elucidate the molecular mechanisms underlying stem cell-driven tumorigenesis and tissue regeneration.

Main Methods:

  • In vivo studies comparing protein synthesis in stem cells and progenitors.
  • Analysis of stress response pathways and translational programs.
  • Investigating the role of post-transcriptional cytosine-5 methylation.

Main Results:

  • Mouse skin stem cells exhibit reduced protein synthesis compared to progenitors, even during proliferation.
  • Activation of stress response pathways globally reduces protein synthesis and alters translational programs, promoting stem cell functions and tumorigenesis.
  • Inhibition of post-transcriptional cytosine-5 methylation sustains this translational inhibition in tumor-initiating cells, paradoxically increasing sensitivity to cytotoxic stress and blocking tumor regeneration.

Conclusions:

  • Protein synthesis reduction and altered translational programs, driven by stress response pathways, are crucial for stem cell function and tumorigenesis.
  • Reversal of translation inhibition is essential for tissue and tumor regeneration after cytotoxic stress.

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