Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells

Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells
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DOI:
10.1038/nbt1335
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发表时间:
2007-10-01
影响因子:
46.9
通讯作者:
Jaenisch, Rudolf
Jaenisch, Rudolf
中科院分区:
工程技术1区
文献类型:
--
作者:
Meissner, Alexander;Wernig, Marius;Jaenisch, Rudolf

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通过用Oct 4、Sox 2、c-myc和Klf 4逆转录病毒转导鼠成纤维细胞,已经实现了体细胞体外重编程为多能胚胎干细胞样状态(参考文献104)。第1-4段)。在这些实验中,通过严格选择插入内源性Oct 4(也称为Pou 5 f1)或Nanog基因座(2-4)的新霉素抗性基因的激活来分离罕见的“诱导多能干细胞”(iPS)。从培养的体细胞中直接分离多能细胞具有潜在的治疗意义,但在本iPS分离方案中对转基因供体的要求将阻碍翻译至人类系统。在这里,我们证明,重编程的多能细胞可以从遗传未修饰的体细胞供体细胞分离,仅基于形态学标准。
In vitro reprogramming of somatic cells into a pluripotent embryonic stem cell-like state has been achieved through retroviral transduction of murine fibroblasts with Oct4, Sox2, c-myc and Klf4 (refs. 1-4). In these experiments, the rare 'induced pluripotent stem' (iPS) cells were isolated by stringent selection for activation of a neomycin-resistance gene inserted into the endogenous Oct4 (also known as Pou5f1) or Nanog loci(2-4). Direct isolation of pluripotent cells from cultured somatic cells is of potential therapeutic interest, but translation to human systems would be hindered by the requirement for transgenic donors in the present iPS isolation protocol. Here we demonstrate that reprogrammed pluripotent cells can be isolated from genetically unmodified somatic donor cells solely based upon morphological criteria.