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tips：iPS細胞是往體細胞中轉入若干基因，使體細胞逆向回到胚胎干細胞樣狀態(tài)，具有多向分化潛能，如可分化成心肌細胞、成骨細胞等，在醫(yī)學上可用患者的自體細胞制成iPS細胞進行機體損傷的組織修復，避免了免疫排斥反應和胚胎干細胞涉及的倫理問題，但目前研究的缺點是可能致瘤。

對體細胞（構成大部分身體組織的“普通”細胞）進行重排、使其成為誘導產(chǎn)生的多能干細胞（iPS細胞）的過程，涉及四個轉錄因子的表達??Oct4、Sox2、 c-Myc和Klf4。為了使這個程序在臨床應用中更簡單、更安全，以減少所需轉基因數(shù)量、免除對致癌基因c-Myc之需要為目的的工作正在進行當中。現(xiàn)在，Kim等人發(fā)現(xiàn)，僅僅兩個內生因子（Oct4 加上Klf4或c-Myc），就足以從成年小鼠神經(jīng)干細胞生成iPS細胞。之所以有可能這樣，是因為這些神經(jīng)細胞比胚胎干細胞表達更高水平的內生Sox2 和 c-Myc，這說明具有適當匹配的轉錄因子的體細胞是生成iPS細胞的一個潛在有用的起始點。

原始出處：

Nature 454, 646-650 (24 July 2008) | doidoi:10.1038/nature07061

Jeong Beom Kim1,3, Holm Zaehres1,3, Guangming Wu1, Luca Gentile1, Kinarm Ko1, Vittorio Sebastiano1, Marcos J. Araúzo-Bravo1, David Ruau2, Dong Wook Han1, Martin Zenke2 & Hans R. Schöler1

Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, R?ntgenstrasse 20, 48149 Münster, NRW, Germany

Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Pauwelsstrasse 30, 52074 Aachen, NRW, Germany

These authors contributed equally to this work.

Correspondence to: Hans R. Schöler1 Correspondence and requests for materials should be addressed to H.R.S. (Email:schoeler@mpi-muenster.mpg.de).

Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4 (refs 1?11). Considering that ectopic expression of c-Myc causes tumorigenicity in offspring2 and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells. These two-factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.