Stem cell function and stress response are controlled by protein synthesis
| Autor: | Roberto Bandiera, Martyna C. Popis, Michaela Frye, Abdulrahim A. Sajini, Sandra Blanco, Nikoletta A. Gkatza, Hinal Tanna, Rosana Cortés-Garrido, Sabine Dietmann, Jelena Aleksic, Patrick Lombard, Shobbir Hussain |
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| Přispěvatelé: | Frye, Michaela [0000-0002-5636-6840], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Skin Neoplasms Cellular differentiation Biology Bioinformatics medicine.disease_cause Methylation Article Cytosine Mice 03 medical and health sciences RNA Transfer Stress Physiological Cellular stress response medicine Animals Humans Regeneration Cytotoxic T cell Progenitor cell Cell Proliferation Multidisciplinary Stem Cells Regeneration (biology) Cell Differentiation Methyltransferases 3. Good health Cell biology Endothelial stem cell Cell Transformation Neoplastic 030104 developmental biology Protein Biosynthesis Neoplastic Stem Cells Female Fluorouracil Stem cell Carcinogenesis Hair Follicle |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature18282 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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