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Bidirectional developmental potential in reprogrammed cells with acquired pluripotency

机译：具有获得性多能性的重编程细胞中的双向发展潜力

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摘要

We recently discovered an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which we call stimulus-triggered acquisition of pluripotency (STAP). This reprogramming does not require nuclear transfer or genetic manipulation. Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues, as seen in a blastocyst injection assay. Mouse STAP cells lose the ability to contribute to the placenta as well as trophoblast marker expression on converting into ES-like stem cells by treatment with adrenocorticotropic hormone (ACTH) and leukaemia inhibitory factor (LIF). In contrast, when cultured with Fgf4, STAP cells give rise to proliferative stem cells with enhanced trophoblastic characteristics. Notably, unlike conventional trophoblast stem cells, the Fgf4-induced stem cells from STAP cells contribute to both embryonic and placental tissues in vivo and transform into ES-like cells when cultured with LIF-containing medium. Taken together, the developmental potential of STAP cells, shown by chi-maera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.
机译：我们最近发现了通过暴露于致死性刺激下的体细胞重编程为多能细胞的意外现象，我们将其称为刺激触发的多能性获得（STAP）。这种重新编程不需要核转移或基因操纵。在这里我们报告说，重编程的STAP细胞与胚胎干（ES）细胞不同，可以对胚胎和胎盘组织都有贡献，如在囊胚注射试验中所见。通过使用促肾上腺皮质激素（ACTH）和白血病抑制因子（LIF）处理，小鼠STAP细胞在转化为ES样干细胞后，丧失了促进胎盘和滋养细胞标志物表达的能力。相反，当与Fgf4培养时，STAP细胞会产生具有增强滋养细胞特性的增殖干细胞。值得注意的是，与传统的滋养层干细胞不同，来自STAP细胞的Fgf4诱导的干细胞在体内对胚胎和胎盘组织都有贡献，并在与含LIF的培养基一起培养时转化为ES样细胞。综上所述，通过嵌合体形成和体外细胞转化显示的STAP细胞的发展潜力表明，它们代表了多能性的独特状态。

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  • 来源
    《Nature》 |2014年第7485期|676-680|共5页
  • 作者

    Haruko Obokata; Yoshiki Sasai; Hitoshi Niwa; Mitsutaka Kadota; Munazah Andrabi; Nozomu Takata; Mikiko Tokoro; Yukari Terashita; Shigenobu Yonemura; Charles A. Vacanti; Teruhiko Wakayama;

  • 作者单位

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

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

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

    Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;

    Genome Resource and Analysis Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;

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

    Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;

    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;

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

  • 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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