Nature2014-06-26 3:58 PM

诱导产生多能性的一个新方式 Stimulus-triggered fate conversion of somatic cells into pluripotency


形成哺乳动物身体主要部分的体细胞的命运被认为主要是由发育的细胞分化过程完成的时间决定的。响应于环境压力的重新编程已在植物中被观察到,但迄今尚未在哺乳动物细胞中被观察到。现在,由Haruko Obokata及同事发表的两篇论文描述了一个出乎意料的重新编程现象,作者将其称作“由刺激触发的多能性获得”(STAP)。在STAP中,小鼠体细胞如CD45+造血细胞因瞬时处于低pH环境而被重新编程为具有多能性。对STAP细胞的分子特征和发育潜力所做的大量分析表明,它们代表着多能性的一个独特状态,并为转录因子的使用提供了另外一个多能细胞来源(此方法已成为生成诱导多能干细胞的常规方法)。


Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells. Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrangement analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection. STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes. Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, our findings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependent manner by strong environmental cues.






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