大鼠是歷史上第一個被馴化用于科學(xué)研究的哺乳動物，用于科研已經(jīng)超過150年,。由于大鼠體型比小鼠大,，手術(shù)操作方便。而且在生理上具有許多獨特的特點,，使得大鼠成為非常好的生物、醫(yī)學(xué),、藥物,、營養(yǎng)、行為等方面研究的良好的模型,，廣泛應(yīng)用于生物醫(yī)藥研究中,。但是迄今為止，仍然沒有大鼠多能的胚胎干細(xì)胞系成功建立的報道,，而多能的胚胎干細(xì)胞是反向遺傳學(xué)研究和制作疾病模型的重要工具,。因此大鼠的遺傳學(xué)研究以及用大鼠制作人類疾病模型的研究都遠(yuǎn)遠(yuǎn)落后于小鼠。
2008年12月18日《細(xì)胞·干細(xì)胞》(Cell Stem Cell)提前在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所博士研究生廖婧和博士后崔春完成的關(guān)于建立和鑒定大鼠誘導(dǎo)多能干細(xì)胞(iPS細(xì)胞)的重要研究工作,，該項工作是在生化與細(xì)胞所研究員肖磊博士指導(dǎo)下完成的,。
在本項工作中,，研究人員成功運(yùn)用病毒表達(dá)轉(zhuǎn)錄因子把大鼠成體細(xì)胞成功地重編程到多能干細(xì)胞狀態(tài)。從數(shù)百個形態(tài)類似胚胎干細(xì)胞的細(xì)胞克隆中,，建立了22個類似胚胎干細(xì)胞的細(xì)胞系,。經(jīng)過進(jìn)一步篩選、鑒定,，最終獲得兩株符合多能干細(xì)胞標(biāo)準(zhǔn)的大鼠iPS細(xì)胞系,。這些細(xì)胞系形態(tài)類似小鼠胚胎干細(xì)胞，具有跟小鼠胚胎干細(xì)胞類似的干細(xì)胞標(biāo)記基因的表達(dá),，而且在體外和體內(nèi)都具有向內(nèi),、中、外三個胚層分化的能力,。
自從1981年小鼠的胚胎干細(xì)胞被建立后,，公認(rèn)的胚胎干細(xì)胞系被報道的哺乳動物只有小鼠、猴和人三個物種,。其他哺乳動物,，包括大鼠以及豬、牛,、羊等,，一直沒有公認(rèn)的胚胎干細(xì)胞系被報道。上述研究結(jié)果第一次原則性地證明了誘導(dǎo)多能干細(xì)胞(iPS)技術(shù)可以為這些歷史上難以建立胚胎干細(xì)胞系的物種建立多能的干細(xì)胞系,；而且這些多能干細(xì)胞有可能直接用于產(chǎn)生基因敲除動物和轉(zhuǎn)基因動物,。這個研究結(jié)果將會促進(jìn)其他物種的誘導(dǎo)多能干細(xì)胞(iPS)研究和應(yīng)用。
這個工作得到了中科院上海生科院生化與細(xì)胞所,、科技部的大力支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Stem Cell, 18 December 2008 doi:10.1016/j.stem.2008.11.013
Generation of Induced Pluripotent Stem Cell Lines from Adult Rat Cells
Jing Liao1,4,Chun Cui1,4,Siye Chen1,Jiangtao Ren1,Jijun Chen1,Yuan Gao1,Hui Li2,Nannan Jia1,Lu Cheng1,Huasheng Xiao3andLei Xiao1,,
1 Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Cell Bank, Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China
2 Xiangtan Center Hospital, Hunan 411100, People's Republic of China
3 National Engineering Center for Biochip at Shanghai, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, People's Republic of China
4 These authors contributed equally to this work
The laboratory rat (Rattus norvegicus) was the first mammalian species domesticated for scientific research, and it has been used as an animal model for physiology, pharmacology, toxicology, nutrition, behavior, immunology, and neoplasia for over 150 years (Jacob, 1999). Despite this history, the rat lags far behind the mouse in functional genetic studies and generation of human disease models because of the absence of functional germline-competent rat embryonic stem cells (ESCs), which are vital in reverse genetics approach. Here, we report the generation of induced pluripotent stem cells (iPSCs) from adult rat cells and demonstrate that the iPSC technique provides a feasible approach to establish pluripotent stem cells for a species in which ESCs have previously proven to be difficult to establish from the early embryo.
After the first mouse ESC lines were derived 27 years ago (Evans and Kaufman, 1981,Martin, 1981), many efforts were made to establish rat ESCs, without success to date (Brenin etal., 1997,Demers etal., 2007,Iannaccone etal., 1994,Mashimo etal., 2008,Schulze etal., 2006,Ueda etal., 2008,Vassilieva etal., 2000). All of the reported cell lines could only be termed ESC-like cells because they did not meet the criteria of ESCs in one or more of the following aspects: (1) few cell lines could proliferate for a long period of time while remaining undifferentiated and maintaining normal karyotypes; (2) an advanced teratoma containing all three germ layers was not reported when the cells were injected into immune-deficient mice, suggesting that these rat ESC-like cells lacked the ability to differentiate into derivatives of all three germ layers; and (3) when rat ESC-like cells were injected into a blastocyst, the cells only contributed to extraembryonic tissue. No convincing evidence was reported that the cells could contribute to other tissues (Brenin etal., 1997,Demers etal., 2007,Ueda etal., 2008). These unsuccessful attempts suggest that establishing rat ESCs from a blastocyst might not be feasible using traditional methods.
