Direct reprogramming of human neural stem cells by OCT4

Direct reprogramming of human neural stem cells by OCT4
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DOI:
10.1038/nature08436
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发表时间:
2009-10-01
期刊:
影响因子:
64.8
通讯作者:
Schoeler, Hans R.
Schoeler, Hans R.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim, Jeong Beom;Greber, Boris;Schoeler, Hans R.

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通过异位表达四种转录因子(OCT4(又称Pou5f1)、SOX2、c-Myc和KLF4)(1-7),从小鼠和人体细胞中获得了诱导多能干细胞(IPS)。我们之前曾报道,仅Oct4就足以将成年小鼠神经干细胞直接重新编程为iPS细胞(8)。在这里,我们报道了由人胚胎神经干细胞(单因素(1F)人NIPS细胞)仅通过异位表达OCT4来产生单因素人iPS细胞。单因子人NIPS细胞在整体基因表达谱、表观遗传状态以及体外和体内的多能性方面与人类胚胎干细胞相似。这些发现表明,转录因子OCT4足以将人类神经干细胞重新编程为多能性。单因素诱导性多能干细胞的产生将进一步推动该领域向理解重新编程和产生患者特有的多能干细胞的方向发展。
Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4)(1-7). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells(8). Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.