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

對(duì)體細(xì)胞（構(gòu)成大部分身體組織的“普通”細(xì)胞）進(jìn)行重排、使其成為誘導(dǎo)產(chǎn)生的多能干細(xì)胞（iPS細(xì)胞）的過(guò)程，涉及四個(gè)轉(zhuǎn)錄因子的表達(dá)??Oct4、Sox2、 c-Myc和Klf4。為了使這個(gè)程序在臨床應(yīng)用中更簡(jiǎn)單、更安全，以減少所需轉(zhuǎn)基因數(shù)量、免除對(duì)致癌基因c-Myc之需要為目的的工作正在進(jìn)行當(dāng)中�，F(xiàn)在，Kim等人發(fā)現(xiàn)，僅僅兩個(gè)內(nèi)生因子（Oct4 加上Klf4或c-Myc），就足以從成年小鼠神經(jīng)干細(xì)胞生成iPS細(xì)胞。之所以有可能這樣，是因?yàn)檫@些神經(jīng)細(xì)胞比胚胎干細(xì)胞表達(dá)更高水平的內(nèi)生Sox2 和 c-Myc，這說(shuō)明具有適當(dāng)匹配的轉(zhuǎn)錄因子的體細(xì)胞是生成iPS細(xì)胞的一個(gè)潛在有用的起始點(diǎn)。

原始出處：

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

Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors

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.

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