哺乳动物的发育始于受精卵,可以分化为胚胎和胚外组织,一种被称为全能性的能力。只有合子基因组激活(ZGA)(小鼠的两细胞胚胎阶段和人类的八细胞胚胎阶段)周围的合子和胚胎是全能细胞。表观遗传修饰在获得全能性和随后的分化发展过程中经历了极其广泛的变化。然而,潜在的分子机制仍然难以捉摸。最近,小鼠双细胞胚胎样细胞的发现,人类八细胞胚胎样细胞,具有胚胎外发育潜能的延伸多能干细胞和全能样干细胞极大地拓展了我们对全能性的理解.这些体外模型的实验导致了对多向全能性重编程中表观遗传变化的见解,这些都为植入前发展的探索提供了信息。在这次审查中,我们强调了在理解全能性捕获过程中表观遗传重塑机制方面的最新发现,包括RNA剪接,DNA甲基化,染色质构型,组蛋白修饰,核组织。
Mammalian development commences with the zygote, which can differentiate into both embryonic and extraembryonic tissues, a capability known as
totipotency. Only the zygote and embryos around zygotic genome activation (ZGA) (two-cell embryo stage in mice and eight-cell embryo in humans) are totipotent cells. Epigenetic modifications undergo extremely extensive changes during the acquisition of
totipotency and subsequent development of differentiation. However, the underlying molecular mechanisms remain elusive. Recently, the discovery of mouse two-cell embryo-like cells, human eight-cell embryo-like cells, extended pluripotent stem cells and totipotent-like stem cells with extra-embryonic developmental potential has greatly expanded our understanding of
totipotency. Experiments with these in vitro models have led to insights into epigenetic changes in the reprogramming of pluri-to-
totipotency, which have informed the exploration of preimplantation development. In this review, we highlight the recent findings in understanding the mechanisms of epigenetic remodeling during
totipotency capture, including RNA splicing, DNA methylation, chromatin configuration, histone modifications, and nuclear organization.