体细胞核移植诱导的表观遗传学变化

Epigenetic modification related to somatic nuclear transfer

体细胞核移植技术是指将一个分化的体细胞核置入去核的卵母细胞中,并发育产生与供体细胞遗传背景一致的克隆后代的技术。目前,世界上通过体细胞核移植技术已经产生了许多的克隆动物。但克隆过程中还存在着很多问题,比如,克隆效率太低、克隆个体常伴有表型异常和早亡等,从而使该技术应有的应用潜力不能得到充分的发挥。体细胞表观遗传学重编程的不完全或紊乱是造成核移植诸多问题的主要原因。近十多年来,人们对体细胞核移植后的重编程进行了广泛的研究,其核心内容包括核及核外结构的重塑、DNA甲基化模式的重建、基因印迹和X染色体失活、组蛋白乙酰化模式的重建、端粒长度恢复等,以期能够对其重编程加以人为干预,从而提高动物克隆效率。本文拟对体细胞核移植诱导的重编程研究进展加以综述,希望对体细胞重编程机制的阐明有所启发。

Somatic cell nuclear transfer is a technology by which a somatic nucleus is put into an enucleated oocyte to make a reconstructed embryo, which subsequently develops to an offspring with the same genetics as donor cells. So far cloned animals have been produced in many species by somatic nuclear transfer. However, there are many problems need to be solved before its potential applications become fully practical, such as low efficiency, abnormal phenotypes and premature death, which are probably caused by incomplete or aberrant epigenetic reprogramming of donor cells. In recent decade, reprogramming after somatic nuclear transfer has been exten- sively studied, mainly focusing on remodeling of structures in or out of nucleus, modification of DNA methylation, X chromosome inactivation, modification of histone acetylation and recovery of telomere length. Those efforts are expected to lead to establish an approach artificially intervening the reprogramming of donor cell in the process of nuclear transfer and eventually improve the efficiency of somatic nuclear transfer.