Stimulus-triggered fate conversion of somatic cells into pluripotency (Retracted article. See vol. 511, pg. 112, 2014)
Stimulus-triggered fate conversion of somatic cells into pluripotency (Retracted article. See vol. 511, pg. 112, 2014)
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DOI：
10.1038/nature12968
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发表时间：
2014-01-30
期刊：
影响因子：
64.8
通讯作者：
Vacanti, Charles A.
中科院分区：
文献类型：
--
作者：
Obokata, Haruko;Wakayama, Teruhiko;Vacanti, Charles A.
在这里，我们报告了一种独特的细胞重编程现象，称为刺激触发获得多能性（STAP），它既不需要核转移，也不需要引入转录因子。在STAP中，强烈的外部刺激，如短暂的低pH应激源重编程哺乳动物体细胞，导致多能细胞的产生。通过对来自纯化淋巴细胞的STAP细胞的实时成像以及基因重排分析，我们发现定向体细胞通过重编程而不是选择产生STAP细胞。STAP细胞显示多能性标记基因调控区的DNA甲基化显著降低。囊胚注射表明，STAP细胞有效地促进嵌合体胚胎和后代通过生殖系传播。我们还证明了从STAP细胞中衍生出稳健可扩增的多能细胞系。因此，我们的研究结果表明，哺乳动物细胞的表观遗传命运决定可以显着转换，在一个上下文依赖的方式由强大的环境线索。
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.