STAP cells are derived from ES cells
STAP cells are derived from ES cells
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STAP细胞来源于ES细胞
DOI：
10.1038/nature15366
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发表时间：
2015
期刊：
影响因子：
64.8
通讯作者：
Matsuzaki F
中科院分区：
文献类型：
--
作者：
Konno D;Kasukawa T;Hashimoto K;Itoh T;Suetsugu T;Miura I;Wakana S;Carninci P;Matsuzaki F
去年1，2，《自然》杂志发表了两篇声称一种新的细胞重编程现象--刺激触发的多能性获取(STAP)，但随后撤回了3，4。然而，STAP细胞和STAP来源的干细胞的身份仍未确定。在这里，我们报告了主要保存在RIKEN发育生物学中心的STAP相关样本的全基因组测序(WGS)调查结果。我们发现，所有声称的STAP干细胞系都被胚胎干细胞(ES)污染，而嵌合体小鼠和畸胎瘤被认为是来自STAP细胞的，而不是ES细胞的贡献。最初的文献1报道，低pH可将分化的细胞重新编程为独特的多能细胞(STAP细胞)，并由此建立两个次级细胞系：ES样STAP干细胞和滋养层干细胞样Fgf4诱导的能够产生胎盘细胞的干细胞1，2。由于STAP细胞没有作为冰冻细胞保存，我们首先对15个基因组DNA样本进行了WGS，其中包括3个具有不同遗传背景的代表性STAP干细胞系，1个Fgf4诱导的干细胞系，以及在STAP研究之前或期间在和歌山实验室建立的7个ES细胞系(扩展数据表1)。我们确定了区分小鼠菌株129/Sv(129)和C57BL/6(B6)的单核苷酸多态(SNPs)以及绿色荧光蛋白(GFP)转基因类型的全基因组模式(补充方法和扩展数据图1A)。没有发现原始字母2中描述的Oct4-GFP Fgf4诱导的干细胞的样本(Oct4也称为Pou5f1)。STAP干细胞系FLS和Fgf4诱导的干细胞系CTS报告携带单个CAG-GFP转基因纯合子插入，遗传背景为129女性3B6男性(扩展数据表1)。然而，这些细胞系共插入了两个GFP转基因基因5，精子特异性顶体酶启动子-gfp6和
Two reports claiming a novel cellular reprogramming phenomenon, stimulus-triggered acquisition of pluripotency (STAP), were published in Nature last year1, 2, but then subsequently retracted3, 4. The identity of STAP cells and STAP-derived stem cells, however, has remained undetermined. Here we report the results of a whole-genome sequencing (WGS) investigation of STAP-related samples kept mainly at the RIKEN Center for Developmental Biology. We show that all purported STAP stem-cell lines were contaminated with embryonic stem (ES) cells, and that chimaeric mice and teratomas supposedly derived from STAP cells instead show ES cell contribution. The original article1 reported that exposure to low pH can reprogram differentiated cells into unique pluripotent cells (STAP cells), from which two secondary cell lines were established; ES-like STAP stem cells and trophoblast stem-like Fgf4-induced stem cells capable of generating placental cells1, 2. Because STAP cells were not maintained as frozen stocks, we first performed WGS of 15 genomic DNA samples in total, including three representative STAP stem-cell lines with different genetic backgrounds, an Fgf4-induced stem-cell line, and seven ES cell lines established at the Wakayama laboratory before or during the STAP study (Extended Data Table 1). We determined genome-wide patterns of single-nucleotide polymorphisms (SNPs) that distinguish mouse strains 129/Sv (129) and C57BL/6 (B6), as well as green fluorescent protein (GFP) transgene types (Supplementary Methods and Extended Data Fig. 1a). No samples from the Oct4-GFP Fgf4-induced stem cells described in the original letter2 were found (Oct4 is also known as Pou5f1).The STAP stem-cell line FLS and the Fgf4-induced stem-cell line CTS were reported to carry a homozygous insertion of a single cag-gfp transgene with the genetic background of 129 female 3 B6 male (Extended Data Table 1). However, these cell lines had co-insertions of two GFP transgenes5, sperm-specific acrosin-promoter-gfp6 and