Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors
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DOI：
10.1016/j.cell.2006.07.024
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发表时间：
2006-08-25
期刊：
影响因子：
64.5
通讯作者：
Yamanaka, Shinya
中科院分区：
文献类型：
--
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
分化的细胞可以通过将核内容物转移到卵母细胞或与胚胎干细胞融合来重新编程为类似胚胎的状态。人们对导致这种重新编程的因素知之甚少。在这里，我们展示了在ES细胞培养条件下，通过引入四种因子，Oct3/4，Sox2，c-Myc和Klf4，从小鼠胚胎或成人成纤维细胞中诱导出多能干细胞。出乎意料的是，Nanog是可有可无的。这些细胞，我们命名为iPS(诱导多能干细胞)，表现出ES细胞的形态和生长特性，并表达ES细胞标记基因。将iPS细胞皮下移植到裸鼠体内，产生了包含所有三个生殖层的各种组织的肿瘤。在注射到囊胚后，iPS细胞有助于小鼠的胚胎发育。这些数据表明，只需添加几个确定的因子，就可以从成纤维细胞培养中直接产生多能干细胞。
Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.