Vc-Jak2-Stat2信号转导途径在体细胞核移植表观重编程中的调控功能

DNA甲基化重编程不完全以及印记基因重编程异常是导致核移植失败的重要因素。维生素C（Vitamin C, Vc）在促进体细胞基因组发生去甲基化的同时，还可以保护和维持印迹正常。我们发现Vc可以激活细胞内Jak2-Stat2信号转导途径，并且以Vc处理的牛成纤维细胞做供核细胞，可以促进体细胞克隆胚胎的发育。在现有研究基础上，申请人推测Vc-Jak2-Stat2途径可能参与了Vc介导的细胞表观重编程调控。因此，本项目申请进一步研究维生素C对牛成纤维细胞表观重编程的调控功能，重点解析和完善Vc作为信号分子在DNA甲基化重编程和印记维持两个方面的调控机制，并揭示Vc诱导的供核细胞重编程对体细胞克隆胚胎发育率提高的作用机理。以上研究不仅可以为进一步揭示细胞重编程机制指引新的方向，还可为家畜体细胞核移植效率的提高提供新的思路和方法，进而加快我国畜牧业良种的培育和扩繁。

Incomplete DNA demethylation and abnormal imprinting in epigenetic reprogramming are the two important factors that lead to the failure of somatic cell nuclear transfer (SCNT). While promotes demethylation of somatic cell genome, Vitamin C（Vc）can also protect and maintain normal imprinting. Our researches indicated that Vc can activate intracellular Jak2-Stat2 signal transduction pathway, and facilitate the development of somatic cloned embryos with Vc-treated bovine fibroblast as donor cells. Based on our existing research, we suggest that Vc-Jak2-Stat2 pathway may function in epigenetic reprogramming induced by vitamin C. Therefore, we apply to this project to further study the regulatory functions of Vc on epigenetic reprogramming in bovine fibroblast cells. We will focus on elucidating the molecular mechanisms of Vc-Jak2-Stat2 pathway in DNA methylation reprogramming and imprinting maintenance, and reveal the mechanism of the increasing development rate of somatic cloned embryos arisen from epigenetic reprogramming in donor cells induced by Vc. These studies not only reveal a new direction for the further research in cell reprogramming mechanism , but also provide new ideas and methods for improving efficiency in livestock nuclear transplantation, thus speeding up livestock breeding and propagation.