Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb
Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb
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DOI：
10.1038/ncb1827
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发表时间：
2009-02-01
影响因子：
21.3
通讯作者：
Ng, Huck-Hui
中科院分区：
文献类型：
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作者：
Feng, Bo;Jiang, Jianming;Ng, Huck-Hui
转录因子在赋予扩大效力方面的主要作用是通过使用逆转录病毒介导的定义转录因子的转导转型转导的成纤维细胞对多能细胞的重编程来体现的。在鼠系统中，OCT4，SOX2，C-MYC和KIF4足以将成纤维细胞转换为具有许多特征的胚胎茎（ES）细胞的诱导多能干（IPS）细胞。在这里，我们表明孤儿核受体ESRR与Oct4和Sox2结合起作用，以介导小鼠胚胎成纤维细胞（MEFS）对IPS细胞的重编程。 ESRRB编程的细胞具有与ES细胞相似的表达和表观遗传特征。这些细胞也具有多能，可以在体外和体内区分三个主要的胚胎细胞谱系。此外，这些细胞有助于小鼠嵌合体，并且是可传播的。在ES细胞中，ESRRB靶向许多参与自我更新和多能性的基因。这表明ESRRB可以通过ES细胞特异性基因的上调介导重编程。我们的发现还表明，可以在没有外源KIF转录因子的情况下重新编程MEF，并将核受体与体细胞重编程联系起来。
The dominant effect of transcription factors in imparting expanded potency is best exemplified by the reprogramming of fibroblasts to pluripotent cells using retrovirus-mediated transduction of defined transcription factors. In the murine system, Oct4, Sox2, c-Myc and KIf4 are sufficient to convert fibroblasts to induced pluripotent stem (iPS) cells that have many characteristics of embryonic stem (ES) cells. Here we show that the orphan nuclear receptor Esrrb functions in conjunction with Oct4 and Sox2 to mediate reprogramming of mouse embryonic fibroblasts (MEFs) to iPS cells. Esrrb-reprogrammed cells share similar expression and epigenetic signatures as ES cells. These cells are also pluripotent and can differentiate in vitro and in vivo into the three major embryonic cell lineages. Furthermore, these cells contribute to mouse chimaeras and are germline transmissible. In ES cells, Esrrb targets many genes involved in self-renewal and pluripotency. This suggests that Esrrb may mediate reprogramming through the upregulation of ES-cell-specific genes. Our findings also indicate that it is possible to reprogram MEFs without exogenous KIf transcription factors and link a nuclear receptor to somatic cell reprogramming.