干细胞的功能和应激反应由蛋白质合成控制
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
概括
细胞应激反应途径减少小鼠皮肤干细胞中的蛋白质合成,促进干细胞功能和瘤生长. 这种抑制必须逆转以使组织或瘤再生.
科学领域:
- 干细胞生物学
- 分子生物学
- 癌症研究
背景情况:
- 干细胞调节中的蛋白质合成和细胞应激反应之间的相互作用尚未得到充分理解.
- 干细胞具有独特的特性,使其能够维持组织平衡并再生受损的组织.
研究的目的:
- 在控制小鼠皮肤干细胞功能的过程中,研究蛋白质合成和细胞应激反应途径之间的相互作用.
- 阐明干细胞驱动的瘤发生和组织再生的分子机制.
主要方法:
- 在体内研究,比较干细胞和祖细胞中的蛋白质合成.
- 分析应激反应途径和转化程序.
- 研究转录后细胞因子-5甲基化的作用.
主要成果:
- 与原始细胞相比,即使在增殖过程中,小鼠皮肤干细胞的蛋白质合成也会减少.
- 激活压力反应通路可以减少蛋白质合成并改变转化程序,促进干细胞功能和瘤发生.
- 抑制转录后的细胞因子-5甲基化维持了这种转化抑制,矛盾地增加了对细胞毒性应激的敏感性,并阻断了瘤再生.
结论:
- 由压力反应途径驱动的蛋白质合成减少和转化程序对于干细胞功能和瘤产生至关重要.
- 在细胞毒性压力后,转化抑制对于组织和瘤再生至关重要.
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