大鼠是历史上第一个被驯化用于科学研究的哺乳动物,用于科研已经超过150年。由于大鼠体型比小鼠大,手术操作方便。而且在生理上具有许多独特的特点,使得大鼠成为非常好的生物、医学、药物、营养、行为等方面研究的良好的模型,广泛应用于生物医药研究中。但是迄今为止,仍然没有大鼠多能的胚胎干细胞系成功建立的报道,而多能的胚胎干细胞是反向遗传学研究和制作疾病模型的重要工具。因此大鼠的遗传学研究以及用大鼠制作人类疾病模型的研究都远远落后于小鼠。
2008年12月18日《细胞·干细胞》(Cell Stem Cell)提前在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所博士研究生廖婧和博士后崔春完成的关于建立和鉴定大鼠诱导多能干细胞(iPS细胞)的重要研究工作,该项工作是在生化与细胞所研究员肖磊博士指导下完成的。
在本项工作中,研究人员成功运用病毒表达转录因子把大鼠成体细胞成功地重编程到多能干细胞状态。从数百个形态类似胚胎干细胞的细胞克隆中,建立了22个类似胚胎干细胞的细胞系。经过进一步筛选、鉴定,最终获得两株符合多能干细胞标准的大鼠iPS细胞系。这些细胞系形态类似小鼠胚胎干细胞,具有跟小鼠胚胎干细胞类似的干细胞标记基因的表达,而且在体外和体内都具有向内、中、外三个胚层分化的能力。
自从1981年小鼠的胚胎干细胞被建立后,公认的胚胎干细胞系被报道的哺乳动物只有小鼠、猴和人三个物种。其他哺乳动物,包括大鼠以及猪、牛、羊等,一直没有公认的胚胎干细胞系被报道。上述研究结果第一次原则性地证明了诱导多能干细胞(iPS)技术可以为这些历史上难以建立胚胎干细胞系的物种建立多能的干细胞系;而且这些多能干细胞有可能直接用于产生基因敲除动物和转基因动物。这个研究结果将会促进其他物种的诱导多能干细胞(iPS)研究和应用。
这个工作得到了中科院上海生科院生化与细胞所、科技部的大力支持。(生物谷Bioon.com)
生物谷推荐原始出处:
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.