Stem cell function and stress response are controlled by protein synthesis

Sandra Blanco, Roberto Bandiera, Martyna Popis, Shobbir Hussain, Patrick Lombard, Jelena Aleksic, Abdulrahim Sajini, Hinal Tanna, Rosana Cortés-Garrido, Nikoletta Gkatza, Sabine Dietmann, Michaela Frye

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalNature
Volume534
Issue number7607
Early online date15 Jun 2016
DOIs
Publication statusPublished - 16 Jun 2016

Fingerprint Dive into the research topics of 'Stem cell function and stress response are controlled by protein synthesis'. Together they form a unique fingerprint.

Cite this