Reprogramming of human somatic cells to pluripotency with defined factors

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.

多能性与早期胚胎的细胞有关，这些细胞能够产生生物体内的所有组织。胚胎干细胞是源自胚胎的细胞系，它们保留了多能性，是研究组织形成机制的极有价值的工具。最近，通过异位表达四种转录因子（Oct4、Sox2、Klf4和Myc），小鼠成纤维细胞已被直接重编程为具有多能性，从而产生诱导多能干细胞（iPS细胞）。利用同样的这些因子，我们已经从胎儿、新生儿和成人的原代细胞中获得了iPS细胞，包括从一名健康研究对象的皮肤活检中分离出的真皮成纤维细胞。人类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上都与胚胎干细胞相似。这些数据表明，特定的因子能够将人类细胞重编程为具有多能性，并建立了一种可能在培养中建立患者特异性细胞的方法。