Hongwei Song, Tiezhu An, Shanhua Piao, Chunsheng Wang
College of Life Science, Northeast Forestry University, Harbin 150040, China.
Yi Chuan. 2014 May;36(5):431-8.
The technology of induced pluripotent stem cell (iPS) provides the possibility to reverse the terminal differentiated cells to pluripotent stem cells, and is therefore of great importance in both the theoretical research of stem cells and regenerative medicine. However, the efficiency of current induced reprogramming methods is extremely low, and the incomplete reprogramming often happens. It has been reported that some epigenetic memory of the somatic cells exists in these incomplete reprogrammed iPS cells, and DNA methylation, as a relative long-term and stable epigenetic modification, is one of the important factors that influence the efficiency of reprogramming and differentiative capacity of iPS cells. Mammalian DNA methylation, which normally appears on the CpG sites, occurs on the fifth carbon atom of the cytosine ring. DNA methylation can modulate the expression of somatic cell specific genes, and pluripotent genes; hence, it plays important roles in the processes of mammalian gene regulation, embryonic development and cell reprogramming. In addition, it has also been found that abnormal DNA methylation may lead to the disorder of genetic imprinting and the inactivation of X chromosome in iPS cells. Therefore, in order to provide a concise guidance of DNA methylation studies in iPS, we mainly review the mechanism, the distribution features of DNA methylation, and its roles in induced reprogramming of somatic cells.
诱导多能干细胞（iPS）技术为将终末分化细胞逆转为多能干细胞提供了可能性，因此在干细胞理论研究和再生医学中都具有重要意义。然而，目前诱导重编程方法的效率极低，且经常发生不完全重编程。据报道，在这些不完全重编程的iPS细胞中存在一些体细胞的表观遗传记忆，而DNA甲基化作为一种相对长期稳定的表观遗传修饰，是影响重编程效率和iPS细胞分化能力的重要因素之一。哺乳动物的DNA甲基化通常出现在CpG位点上，发生在胞嘧啶环的第五个碳原子上。DNA甲基化可以调节体细胞特异性基因和多能基因的表达；因此，它在哺乳动物基因调控、胚胎发育和细胞重编程过程中发挥着重要作用。此外，还发现异常的DNA甲基化可能导致iPS细胞中基因印记紊乱和X染色体失活。因此，为了为iPS中DNA甲基化研究提供简要指导，我们主要综述了DNA甲基化的机制、分布特征及其在体细胞诱导重编程中的作用。
