Reprogramming of human somatic cells to pluripotency with defined factors

Reprogramming of human somatic cells to pluripotency with defined factors
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DOI:
10.1038/nature06534
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发表时间:
2008-01-10
期刊:
影响因子:
64.8
通讯作者:
Daley, George Q.
Daley, George Q.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Park, In-Hyun;Zhao, Rui;Daley, George Q.

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多能性是指早期胚胎的细胞可以产生生物体中的所有组织。胚胎干细胞是胚胎来源的细胞系,保留了多能性,并代表了研究组织形成机制的宝贵工具。最近,鼠成纤维细胞已经通过四种转录因子(Oct4、Sox2、Klf4和Myc)的异位表达被直接重编程为多能性,以产生诱导的多能干(iPS)细胞。使用这些相同的因子,我们已经从胎儿、新生儿和成年人的原代细胞中获得了iPS细胞,包括从健康研究对象的皮肤活检中分离的真皮成纤维细胞。人iPS细胞在形态和基因表达方面以及在免疫缺陷小鼠中形成畸胎瘤的能力方面类似于胚胎干细胞。这些数据表明,确定的因子可以将人细胞重编程为多能性,并建立了一种方法,由此可以在培养物中建立患者特异性细胞。
Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo- derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors ( Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem ( iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune- deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient- specific cells might be established in culture.