1] Laboratory for Cellular Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [2] Laboratory for Genomic Reprogramming, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan [3] 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.
Nature. 2014 Jan 30;505(7485):676-80. doi: 10.1038/nature12969.
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 chimaera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.
我们最近发现了一种意想不到的现象，即体细胞在亚致死刺激下被重编程为多能细胞，我们称之为刺激触发获得多能性（STAP）。这种重编程不需要核转移或基因操作。在这里，我们报告说，与胚胎干细胞（ES 细胞）不同，重编程的 STAP 细胞可以在胚胎和胎盘组织中发挥作用，如在囊胚注射试验中所见。当用促肾上腺皮质激素（ACTH）和白血病抑制因子（LIF）处理时，小鼠 STAP 细胞失去了向胎盘以及滋养层标记物表达贡献的能力，转化为 ES 样干细胞。相比之下，当用 Fgf4 培养时，STAP 细胞产生具有增强的滋养层特征的增殖性干细胞。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向胚胎和胎盘组织中发挥作用，并在含有 LIF 的培养基中培养时转化为 ES 样细胞。总之，嵌合体形成和体外细胞转化所显示的 STAP 细胞的发育潜力表明它们代表了一种独特的多能状态。
