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Stem cell function and sensitivity to genotoxic stress is controlled by protein translation rates

GSE72067 Mus musculus Methylation profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing; Expression profiling by high throughput sequencing; Other 28 samples Submitted 2016/06/16 Platform GPL9250
Summary
Whether protein synthesis and cellular stress response pathways interact to control stem cell functions is currently unknown. Here, we show that skin stem cells synthesise less protein than their immediate progenitors in vivo, even when forced to proliferate in a tumour model. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translation of specific mRNAs that together promote stem cell functions and tumourigenesis. Mechanistically we show that inhibition of post-transcriptional cytosine-5 methylation locks stem cells in this distinct translational inhibition programme. Paradoxically, this stress-induced translation inhibition renders stem cells hypersensitive to genotoxic 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.
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Direct links to NCBI, no account and no request form: the whole study as GSE72067_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA292860 and SRA study SRP062408. Searching any of these in the dataset finder brings you back here.

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