Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Curr Top Dev Biol. 2018;128:203-235. doi: 10.1016/bs.ctdb.2017.10.011. Epub 2017 Nov 20.
When reflecting about cell fate commitment we think of differentiation. Be it during embryonic development or in an adult stem cell niche, where cells of a higher potency specialize and cell fate decisions are taken. Under normal circumstances this process is definitive and irreversible. Cell fate commitment is achieved by the establishment of cell-type-specific transcriptional programmes, which in turn are guided, reinforced, and ultimately locked-in by epigenetic mechanisms. Yet, this plunging drift in cellular potency linked to epigenetically restricted access to genomic information is problematic for reproduction. Particularly in mammals where germ cells are not set aside early on like in other species. Instead they are rederived from the embryonic ectoderm, a differentiating embryonic tissue with somatic epigenetic features. The epigenomes of germ cell precursors are efficiently reprogrammed against the differentiation trend, only to specialize once more into highly differentiated, sex-specific gametes: oocyte and sperm. Their differentiation state is reflected in their specialized epigenomes, and erasure of these features is required to enable the acquisition of the totipotent cell fate to kick start embryonic development of the next generation. Recent technological advances have enabled unprecedented insights into the epigenetic dynamics, first of DNA methylation and then of histone modifications, greatly expanding the historically technically limited understanding of this processes. In this chapter we will focus on the details of embryonic epigenetic reprogramming, a cell fate determination process against the tide to a higher potency.
当我们思考细胞命运决定时,会想到分化。无论是在胚胎发育过程中还是在成人干细胞龛中,高潜能细胞都会特化,细胞命运决定也随之发生。在正常情况下,这个过程是确定且不可逆的。细胞命运决定是通过建立细胞类型特异性转录程序来实现的,而这些程序反过来又受到表观遗传机制的指导、强化和最终锁定。然而,这种与表观遗传限制获得基因组信息相关的细胞潜能急剧下降,对生殖造成了问题。在哺乳动物中尤其如此,因为与其他物种不同,生殖细胞不会很早就被分离出来。相反,它们是从胚胎外胚层重新衍生而来的,而胚胎外胚层是一种具有体细胞表观遗传特征的分化胚胎组织。生殖细胞前体的表观基因组有效地对抗分化趋势进行重新编程,只是为了再次特化为高度分化的、性别的特异性配子:卵子和精子。它们的分化状态反映在它们特化的表观基因组中,为了能够获得全能性细胞命运,从而启动下一代的胚胎发育,这些特征需要被抹去。最近的技术进步使我们能够以前所未有的方式深入了解表观遗传动力学,首先是 DNA 甲基化,然后是组蛋白修饰,极大地扩展了对这一过程的历史上技术有限的理解。在本章中,我们将重点介绍胚胎表观遗传重编程的细节,这是一种与更高潜能相反的细胞命运决定过程。