Embryonic stem (ES) cells, derived from the inner cell mass of mammalian blastcysts, have the ability to grow indefinitely while maintaining pluripotency (Evans and Kaufman, 1981; Martin, 1981). These properties have led to expeсtations that human ES cells might be useful to understand disease mechanisms, to screen effective and safe drugs, and to treat patients of various diseases and injuries, such as juvenile diabetes and spinal cord injury(Thomson et al. ,1998). Use of human embryos, however, faces ethical controversies that hinder the applications of human ES cells. In addition, it is difficult to generate patient- or disease specific ES cells, which are required for their effective application. One way to circumvent these issues is to induce pluripotent status in somatic cells by direct reprogramming (Yamanaka、 2007).

We showed that induced pluripotent stem (iPS) cells can be generated from mouse embryonic fibroblasts (MEF) and adult mouse tail-tip fibroblasts by the retrovirus-mediated transfection of four transcription factors, namely Oct3/4.

Sox2, с-Myc, and Klf4 (Takahashi and Yamanaka.2006). Mouse iPS cells are in distinguishable from ES cells in morphology, proliferation, gene expression, and teratoma formation. Furthermore, when transplanted into blastocysts, mouse iPS cells can give rise to adult chimeras, which are competent for germline transmission (Maberali et al..2007; Okita et al.，2007; Wernig et al.,2007). These results are proof of principle that pluripotent stem cells can be generated from somatic cells by the combination of a small number of factors.

In the current study, we sought to generate iPS cells from adult human somatic cells by optimizing retroviral transduction in human fibroblasts and subsequent culture conditions. These efforts have enabled us to generate iPS cells from adult human dermal fibroblasts and other human somatic cells, which are comparable to human ES cells in their differentiation potential in vitro and in teratomas.

                                                                                 [《Cell》,2007;(131). 861--872]

参考译文

胚胎干细胞来自干哺乳动物胚泡内细胞团块，它具有无限生长的能力并且可以保持多向分化潜能。这些特性让我们有希望通过胚胎干细胞的研究来了解疾病的发病机制，从而可以用于筛选安全有效的药物，治疗不同病损的患者，比如青少年糖尿病和脊髓损伤。然而，人类胚胎的使用面临着许多伦理的争论。这些争论阻碍了人类胚胎干细胞的应用。另外，培养出特定患者或特定疾病的胚胎干细胞是很困难的，但这却是它们的有效应用所必需的。避免这些问题的一种办法是通过直接的重编程诱导体细胞成为多能状态。

我们通过逆转录病毒转染 Oct3/4, Sox2，c-Myc和KIf4等四个转录因子将小鼠胚胎成纤维细胞和成鼠鼠尾成纤维细胞转变为诱导的多能干细胞(iPS)。小鼠的这种诱导多能干细胞在形态、增殖、基因表达和畸胎瘤形成方面与胚胎干细胞并无差别。而且，我们将这种诱导多能干细胞移植入胚泡后能够产生具有种系遗传能力的成年嵌合体老鼠。这些结果证明通过少数因子的组合可以将体细胞变为多能干细胞。

在最近的研究中，我们试图在人成纤维细胞和随后的培养条件中通过最优化的逆转录病毒转染将人的体细胞转变为诱导的多能干细胞。我们可通过上述工作将人的皮肤成纤维细胞和其他体细胞转变为诱导的多能干细胞，而这些干细胞在体外和体内的分化潜能可以和人的胚胎干细胞相媲美。

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