摘要:
Cell reprogramming refers to the transformation of gene expression within a cell from one type to another,and that is defined as the converting process of somatic cells to pluripotent or totipotent stem cell by differentiation or to another type of somatic cells by transdifferentiation under certain conditions. Cell reprogramming provides infinite cell resources for clinical patient-specific cell therapy. It can be achieved by somatic cell nuclear transfer,transfecting specific transcription factor,and induction with small molecule compounds. However,the somatic nuclear transfer technique is thought to have ethical issues because of using oocytes ;and the integration of transcription factor into the host genome leads to gene mutations,which greatly limits their clinical application. Small molecule compounds are easy to be synthesized,have fine cell permeability and flexible biological effects. The use of small molecule compounds to induce cell reprogramming avoids the ethical issues from nuclear transfer the potential harm from gene manipulation. At present,the small molecule compounds are used to induce safer iPSCs(induced pluripotent stem cells),ciCMs(chemically induced functional cardiomyocyte cells),and ciNSLCs(chemical-induced neural stem cell-like cells)from somatic cells. Here we summarize different kinds of cell identity conversions induced by small molecule compounds,referring to induced pluripotent stem cells,induced extended pluripotent stem cells and induced cell transdifferentiation,and finally prospect the future development of induction by small molecule compounds,the purpose is to provide reference for future research in this field.%细胞重编程指细胞内的基因表达由一种类型转变为另一种类型,通常包含两层含义:一是分化的细胞重新恢复到多能性或全能性状态;二是从一种分化的细胞转变为另一种分化的细胞.细胞重编程可为临床患者特异性细胞治疗提供无限的细胞资源.细胞重编程的途径有细胞核移植、转染特定转录因子、小分子化合物诱导等方法.核移植技术由于通常需要使用到卵子,而被认为存在伦理问题;转录因子的导入存在引起宿主基因突变的问题,限制了这一技术的临床应用.然而小分子化合物容易合成、细胞渗透性好,并且生物效应具有可塑性,使用小分子化合物诱导细胞重编程,避免了核移植的伦理问题和基因操作潜在的危害.目前,使用小分子化合物从体细胞诱导获得更安全的iPSCs(induced pluripotent stem cells),ciCMs(chemically induced functional cardiomyocyte cells)和ciNSLCs(chemical-induced neural stem cell-like cells).对小分子化合物诱导细胞重编程,包括小分子化合物诱导多能干细胞;小分子化合物诱导潜能扩展的多能干细胞,以及小分子化合物诱导细胞转分化等方面的研究做了总结,并对小分子化合物诱导的未来发展做了展望,旨在为今后这方面的研究提供借鉴.