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]

參考譯文

胚胎干細(xì)胞來自干哺乳動物胚泡內(nèi)細(xì)胞團(tuán)塊，它具有無限生長的能力并且可以保持多向分化潛能。這些特性讓我們有希望通過胚胎干細(xì)胞的研究來了解疾病的發(fā)病機制，從而可以用于篩選安全有效的藥物，治療不同病損的患者，比如青少年糖尿病和脊髓損傷。然而，人類胚胎的使用面臨著許多倫理的爭論。這些爭論阻礙了人類胚胎干細(xì)胞的應(yīng)用。另外，培養(yǎng)出特定患者或特定疾病的胚胎干細(xì)胞是很困難的，但這卻是它們的有效應(yīng)用所必需的。避免這些問題的一種辦法是通過直接的重編程誘導(dǎo)體細(xì)胞成為多能狀態(tài)。

我們通過逆轉(zhuǎn)錄病毒轉(zhuǎn)染 Oct3/4, Sox2，c-Myc和KIf4等四個轉(zhuǎn)錄因子將小鼠胚胎成纖維細(xì)胞和成鼠鼠尾成纖維細(xì)胞轉(zhuǎn)變?yōu)檎T導(dǎo)的多能干細(xì)胞(iPS)。小鼠的這種誘導(dǎo)多能干細(xì)胞在形態(tài)、增殖、基因表達(dá)和畸胎瘤形成方面與胚胎干細(xì)胞并無差別。而且，我們將這種誘導(dǎo)多能干細(xì)胞移植入胚泡后能夠產(chǎn)生具有種系遺傳能力的成年嵌合體老鼠。這些結(jié)果證明通過少數(shù)因子的組合可以將體細(xì)胞變?yōu)槎嗄芨杉?xì)胞。

在最近的研究中，我們試圖在人成纖維細(xì)胞和隨后的培養(yǎng)條件中通過最優(yōu)化的逆轉(zhuǎn)錄病毒轉(zhuǎn)染將人的體細(xì)胞轉(zhuǎn)變?yōu)檎T導(dǎo)的多能干細(xì)胞。我們可通過上述工作將人的皮膚成纖維細(xì)胞和其他體細(xì)胞轉(zhuǎn)變?yōu)檎T導(dǎo)的多能干細(xì)胞，而這些干細(xì)胞在體外和體內(nèi)的分化潛能可以和人的胚胎干細(xì)胞相媲美。

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