小鼠胚胎干细胞中2C-like细胞研究进展  

Review on 2C-like state of mouse embryonic stem cells

作　　者：王艳秋 包斯琴 吴宝江 Yanqiu Wang;Siqin Bao;Baojiang Wu(Research Center for Animal Genetic Resources of Mongolia Plateau,College of Life Sciences,Inner Mongolia University,Hohhot 010020,China)

机构地区：[1]内蒙古大学生命科学学院,蒙古高原动物遗传资源研究中心,呼和浩特010020

出　　处：《科学通报》2021年第33期4231-4239,共9页Chinese Science Bulletin

基　　金：国家自然科学基金(32060176);内蒙古大学高层次人才引进科研启动金(10000-21311201/058);内蒙古自治区自然科学基金(2021MS03003)资助。

摘　　要：小鼠胚胎干细胞(embryonic stem cell, ESC)由小鼠囊胚的内细胞团体外培养获得.小鼠胚胎干细胞可贡献到胚胎的3个胚层,但缺乏形成胚外组织的能力,因此,小鼠胚胎干细胞被认为具有多能性(pluripotent),而不是全能性(totipotent).值得注意的是,小鼠胚胎干细胞中含有少量的亚细胞群(小于1%),其基因表达模式类似2-细胞期胚胎,这一类细胞称为2-细胞期胚胎样细胞(2-cell embryo like cell, 2C-like cell).在适当的体外培养条件下,小鼠胚胎干细胞和诱导多能性干细胞(induced pluripotent stem cell, iPSC)中均会自发产生少量的2C-like细胞. 2C-like细胞具有全能性和独特的发育特性,嵌合体实验证明其可同时贡献到胚胎和胚外组织中,因此2C-like细胞可以作为体外研究全能性干细胞的理想模型.本文就2C-like细胞的发现、分子调控机制、染色质特征、激活策略以及与体细胞重编程之间的关系等进行综述.Mouse embryonic stem cells(ESCs) are derived from the inner cell mass of mouse blastocysts. Mouse ESCs are pluripotent and contribute widely to the formation of the three embryonic germ layers in chimeric mice but not to that of the extraembryonic trophectoderm. A small population of transient cells(less than 1%) has been identified occasionally in the culture of mouse ESCs, which has been shown to exhibit a gene expression profile similar to that of cells in 2-cell stage embryos(2C-like cells). 2C-like cells were found to be generated spontaneously from mouse ESCs and induced pluripotent stem cells(iPSCs) when they were cultured in the serum-supplemented with leukemia inhibitory factor(LIF) on feeder cells in vitro. 2C-like cells have been considered to be totipotent. There is evidence suggesting that 2C-like cells can effectively generate both embryonic and extra-embryonic tissues, and therefore, 2C-like cells can be potentially used as a model for in vitro totipotent stem cell research. However, only a small population of ESCs could transit to 2C-like state in the serum-containing culture medium. There are several 2C specific genes that express when ESCs enter 2C-like state, such as Zscan4, Mervl, Dux, Nelfa, Tdpoz1/2/4 and Tcstv1/3. Notably, 2C-like cells exhibit highly relaxed chromatin architecture, which is similar to that observed in 2-cell stage embryos. Genome-wide demethylation occurs upon transition of mouse ESCs into 2C-like state, including gene bodies, promoters, and repeat elements. The dynamics of the reprogramming process from ESCs to 2C-like cells are still unclear, which have certainly uncovered an intricate regulatory mechanism mediated by specific genes, proteins, as well as some metabolites and non-coding RNAs.Additionally, one of the important features of totipotency is that a single cell can form an entire organism. Therefore,totipotent stem cells form a valuable tool to study the early developmental processes in vitro and prove to be beneficial for regenerative medicine applications. For

关 键 词：哺乳动物 全能性 合子基因组激活 胚胎干细胞 2C-like细胞 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]