Stem cell function and stress response are controlled by protein synthesis

被引：390

作者：

Blanco, Sandra ^{[1
]}

Bandiera, Roberto ^{[1
]}

Popis, Martyna ^{[1
]}

Hussain, Shobbir ^{[2
]}

Lombard, Patrick ^{[1
]}

Aleksic, Jelena ^{[1
]}

Sajini, Abdulrahim ^{[1
]}

Tanna, Hinal ^{[3
]}

Cortes-Garrido, Rosana ^{[1
]}

Gkatza, Nikoletta ^{[1
]}

Dietmann, Sabine ^{[1
]}

Frye, Michaela ^{[1
]}

机构：

[1] Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Dept Genet, Cambridge CB2 1QR, England

[2] Univ Bath, Dept Biol & Biochem, Claverton Down, Bath BA2 7AY, Avon, England

[3] Univ Cambridge, CR UK, Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England

来源：

NATURE | 2016年 / 534卷 / 7607期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

OPEN READING FRAMES; METHYLTRANSFERASE MISU NSUN2; RNA METHYLTRANSFERASE; GENE-EXPRESSION; MESSENGER-RNA; TRANSLATIONAL REGULATION; TGF-BETA; IN-VIVO; METHYLATION; IDENTIFICATION;

D O I：

10.1038/nature18282

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

收藏

页码：335 / +

页数：20

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