Efficient reprogramming of human and mouse primary extra-embryonic cells to pluripotent stem cells
Efficient reprogramming of human and mouse primary extra-embryonic cells to pluripotent stem cells
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DOI：
10.1111/j.1365-2443.2009.01356.x
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发表时间：
2009-12-01
期刊：
影响因子：
2.1
通讯作者：
Tada, Takashi
中科院分区：
文献类型：
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作者：
Nagata, Shogo;Toyoda, Masashi;Tada, Takashi
目前诱导多能干细胞（iPSC）技术的实际临床应用受到非常低的生成效率的阻碍。在这里，我们证明了新生人类（h）和小鼠（m）胚胎外羊膜（AM）和卵黄囊（YS）细胞（其中表达内源性KLF 4/Klf 4、c-MYC/c-Myc和RONIN/Ronin）可以重编程为hiPSC和miPSC，AM细胞的效率分别为0.02%和0.1%。hiPSC和miPSC两者在集落形态、多能性标志物的表达、全局基因表达谱、0 CT 4和NANOG的DNA甲基化状态、畸胎瘤形成以及在miPSC的情况下生殖系可传递嵌合小鼠的产生方面与胚胎干细胞不可区分。由于大量的人AM细胞可以在没有侵入的情况下收集，并且通过常规手段长期储存而不需要体外培养，因此它们代表了用于细胞库和随后“按需”产生用于个人再生和药物应用的hiPSC的理想来源。
Practical clinical applications for current induced pluripotent stem cell (iPSC) technologies are hindered by very low generation efficiencies. Here, we demonstrate that newborn human (h) and mouse (m) extra-embryonic amnion (AM) and yolk-sac (YS) cells, in which endogenous KLF4/Klf4, c-MYC/c-Myc and RONIN/Ronin are expressed, can be reprogrammed to hiPSCs and miPSCs with efficiencies for AM cells of 0.02% and 0.1%, respectively. Both hiPSC and miPSCs are indistinguishable from embryonic stem cells in colony morphology, expression of pluripotency markers, global gene expression profile, DNA methylation status of OCT4 and NANOG, teratoma formation and, in the case of miPSCs, generation of germline transmissible chimeric mice. As copious amounts of human AM cells can be collected without invasion, and stored long term by conventional means without requirement for in vitro culture, they represent an ideal source for cell banking and subsequent 'on demand' generation of hiPSCs for personal regenerative and pharmaceutical applications.