诱导性多能干细胞构建策略及其提高重编程效率的方法  

Progress on Strategy of Generating Induced Pluripotent Stem Cells and Its Methods of Increasing Reprogramming Efficiency

作　　者：李佳佳[1] 马利兵[1] 陈秀莉[1,2] 籍凤宇[1,3] 

机构地区：[1]内蒙古科技大学数理与生物工程学院,包头014010 [2]包头师范学院生物科学与技术学院,包头014030 [3]包头医学院第一附属医院,包头014010

出　　处：《生物技术通报》2012年第7期41-48,共8页Biotechnology Bulletin

基　　金：国家自然科学基金项目(31160245);内蒙古自治区自然科学基金项目(2009BS0503);内蒙古自治区高等学校科学技术研究项目(NJ09093);内蒙古科技大学创新基金项目(2009NC058)

摘　　要：以Oct4、Sox2、Klf4和c-Myc等转录因子于体细胞中异位表达,可获得具有胚胎干细胞特性的诱导性多能干细胞(iPSCs),但是iPSCs技术的重编程效率和应用于临床上的安全性却都很低。目前,iPSCs的研究集中于3个方面:一是增加iPSCs技术的重编程效率;二是增加iPSCs应用于临床时的安全性;三是开创新的构建iPSCs的方法。第一个方面通过调整体细胞的表观遗传特性和细胞信号网络来达到;第二个方面可通过减少致癌性因子的使用及选择合适的载体系统来达到。而且,一些小分子化合物和调节细胞信号网络的方法也被用于诱导体细胞重编程为iPSCs。相对于仅仅使用转录因子重编程体细胞为iPSCs,使用小分子化合物或调节细胞信号网络的方法重编程体细胞为iPSCs的效率更高,而且通过这种方法获得的iPSCs的有更高的临床安全性。新构建iPSCs的方式与依赖含转录因子表达载体构建iPSCs的传统模式区别较大,它们的临床安全性或(和)重编程效率也得到了极大提高。使用4个转录因子的重组蛋白或体外合成并修饰的转录因子的mRNA已经能成功构建iPSCs;而使用miRNAs高效率重编程小鼠和人的体细胞为iPSCs的方法则开创了脱离转录因子重编程体细胞的全新策略。The technology of induced pluripotent stem cells （ iPSCs ） , in which embryonic-like stem cell can be obtained by ectopic expression of transcription factors, which are Oct4, Sox2, Klf4, and c-Myc separately, have low reprogramming efficiency, and the safety of iPSCs applied in the clinic is compromised. In present, the researches on iPSCs focus on three aspects, one is increasing the efficiency of iPSCs technology ; the other is improving the safety of iPSCs applied in the clinic ; the last one is inaugurating new strategy of generating iPSCs. The first aspect can be achieved by regulating the epigenetic traits and the signaling network of somatic cells ; the second aspect can be achieved by reducing ectopic expression of carcinogenic factors, alternatively, applying suitable vector system. Moreover, some kinds of small molecule chemicals and means of adjusting cellular signaling network can also be used to reprogram somatic cells into iPSCs. Compared with reprogramming somatic cells by transcription factors, reprogramming somatic cells by small molecule chemicals or means of adjusting cellular signaling network has high efficiency, and the iPSCs derived from this approach also has high clinic safety. There is a big difference between the traditional mode of transcription factor-based cellular reprogramming and the new strategies of generating iPSCs which aslo have high efficiency and （ or ） clinic safety. Generation of iPSCs using recombinant proteins of four transcription factors or using synthetic modified mRNA of some transcription factors has been successful. The method of highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to iPSCs inaugurates a new strategy of cellular reprogramming independence of transcription factors.

关 键 词：诱导性多能干细胞 转录因子 载体系统 重编程效率 安全性 全新策略 

分 类 号：Q813[生物学—生物工程]