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Stimulus-triggered fate conversion of somatic cells into pluripotency

机译：刺激触发的将体细胞转化为多能性的命运

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摘要

形成哺乳动物身体主要部分的体细胞的命运rn被认为主要是由发育的细胞分化过程完成的rn时间决定的。响应于环境压力的重新编程已rn在植物中被观察到，但迄今尚未在哺乳动物rn细胞中被观察到。现在，由Haruko Obokatarn及同事发表的两篇论文描述了一个出乎意料rn的重新编程现象，作者将其称作“由刺激触rn发的多能性获得”(STAP)。在STAP中，小鼠rn体细胞如CD45+造血细胞因瞬时处于低pH环rn境而被重新编程为具有多能性。%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 germime 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.
机译：形成哺乳动物身体主要部分的体细胞的命运rn被认为主要是由发育的细胞分化过程完成的rn时间决定的。响应于环境压力的重新编程已rn在植物中被观察到，但迄今尚未在哺乳动物rn细胞中被观察到。现在，由Haruko Obokatarn及同事发表的两篇论文描述了一个出乎意料rn的重新编程现象，作者将其称作“由刺激触rn发的多能性获得”(STAP)。在STAP中，小鼠rn体细胞如CD45+造血细胞因瞬时处于低pH环rn境而被重新编程为具有多能性。%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 germime 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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  • 来源
    《Nature》 |2014年第7485期|641-647a11|共8页
  • 作者

    Haruko Obokata; Teruhiko Wakayama; Yoshiki Sasai; Koji Kojima; Martin P. Vacanti; Hitoshi Niwa; Masayuki Yamato; Charles A. Vacanti;

  • 作者单位

    Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA,Laboratory for Cellular Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan,Laboratory for Genomic Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan;

    Laboratory for Genomic Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan,Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan;

    Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental biology, Kobe 650-0047, Japan;

    Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA,Department of Pathology, Irwin Army Community Hospital, Fort Riley, Kansas 66442, USA;

    Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental biology, Kobe 650-0047, Japan;

    Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo 162-8666, Japan;

    Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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