Abstract:
The nucleolus is the most prominent liquid droplet-like membrane-less organelle in mammalian cells. Unlike the nucleolus in terminally differentiated somatic cells, those in totipotent cells, such as murine zygotes or two-cell embryos, have a unique nucleolar structure known as nucleolus precursor bodies (NPBs). Previously, it was widely accepted that NPBs in zygotes are simply passive repositories of materials that will be gradually used to construct a fully functional nucleolus after zygotic genome activation (ZGA). However, recent research studies have challenged this simplistic view and demonstrated that functions of the NPBs go beyond ribosome biogenesis. In this review, we provide a snapshot of the functions of NPBs in zygotes and early two-cell embryos in mice. We propose that these membrane-less organelles function as a regulatory hub for chromatin organization. On the one hand, NPBs provide the structural platform for centric and pericentric chromatin remodelling. On the other hand, the dynamic changes in nucleolar structure control the release of the pioneer factors (i.e. double homeobox (Dux)). It appears that during transition from totipotency to pluripotency, decline of totipotency and initiation of fully functional nucleolus formation are not independent events but are interconnected. Consequently, it is reasonable to hypothesize that dissecting more unknown functions of NPBs may shed more light on the enigmas of early embryonic development and may ultimately provide novel approaches to improve reprogramming efficiency.
摘要:
核仁是哺乳动物细胞中最突出的液滴状无膜细胞器。与终末分化体细胞的核仁不同,全能细胞中的那些,如鼠受精卵或双细胞胚胎,具有独特的核仁结构,称为核仁前体体(NPBs)。以前,人们普遍认为,受精卵中的NPBs只是材料的被动存储库,这些材料将在合子基因组激活(ZGA)后逐渐用于构建功能齐全的核仁。然而,最近的研究对这种简单的观点提出了挑战,并证明NPBs的功能超出了核糖体生物发生的范围。在这次审查中,我们提供了受精卵和小鼠早期双细胞胚胎中NPBs功能的快照。我们建议这些无膜细胞器充当染色质组织的调节中心。一方面,NPB为中心染色质重塑和外周染色质重塑提供了结构平台。另一方面,核仁结构的动态变化控制着先驱因子(即双同源盒(Dux))的释放。似乎在从全能性到多能性的转变过程中,全能性的下降和全功能核仁形成的开始不是独立的事件,而是相互关联的。因此,有理由假设解剖NPBs的更多未知功能可能会进一步揭示早期胚胎发育的谜团,并可能最终提供新的方法来提高重编程效率。