RNA末端转移酶Star-PAP对胚胎干细胞休眠状态的调控作用及机制研究

休眠状态是近来发现的一种全新的胚胎干细胞存在状态。此状态下细胞生长停滞但依然维持多能干性，打破了长期以来人们对于胚胎干细胞多能性依赖于细胞快速增殖的固有认识。申请人前期工作中发现RNA末端转移酶Star-PAP可能参与调控胚胎干细胞休眠状态的转换，但其具体的分子机制以及在胚胎发育中的作用仍未知。本项目拟利用胚胎干细胞系统研究Star-PAP在休眠状态转换中的作用；探寻并鉴定其调控的下游靶基因；构建敲除小鼠模型研究其对胚胎发育的影响；最后探讨Star-PAP调控靶基因RNA的具体机制。本项目旨在鉴定新的调控休眠状态转换的关键基因，揭示其调控的分子机理，阐明其在胚胎发育中的重要作用。在为解析休眠状态的分子调控网络奠定基础的同时，也给胚胎发育的细胞和分子机制研究提供思路。

Dormant state is a new ES cells state found recently, in which cell growth is paused but its pluripotency and competent are still remained. This discovery has broken the inherent cognitive—pluripotency of ES cells depends on rapid cell proliferation. Previously, we have found that RNA-terminal transferase Star-PAP may be involved in the regulation of ES cells dormant state transition. However, the role of Star-PAP in this transition as well as in embryonic development is still unknown. To illuminate the function of Star-PAP in ES cells state transition, we will identify its downstream target genes, establish the Star-PAP knockout mouse model and explore the regulation mechanisms of Star-PAP to its target mRNA by using the ES cell system. This study aims to identify new key genes in regulating the dormancy transition, and to elucidate the role of Star-PAP in this transition and in embryonic development. This research can not only establish foundation for the molecular regulatory networks of ES cells’ dormant state, but also provides ideas for the cellular and molecular mechanisms of embryonic development.