维生素C促进猪pre-iPSC阶段到iPSC阶段重编程过程中DNA甲基化的变化

项目名称： 维生素C促进猪pre-iPSC阶段到iPSC阶段重编程过程中DNA甲基化的变化

项目编号： No.31301970

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 农业科学

项目作者： 殷玉鹏

作者单位： 西北农林科技大学

项目金额： 23万元

中文摘要： 目前iPSC诱导效率低和质量不好是其应用到临床治疗的一个瓶颈。普遍认为导致iPSC效率低的一个主要原因是在体细胞完全重编程的过程中要经历一个pre-iPSC阶段，只有体细胞绕过该阶段才能进行完全重编程。Vc通过调节组蛋白去甲基化酶Jhdm1a 和 Jhdm1b 的活性来维持 Dlk1-Dio3 印迹，进而促进iPSC达到完全重编程的状态。Vc可能促进Tet家族成员羟化5mC成为5hmC，或许是Vc促进体细胞重编程的一种潜在机制。本项目在我们已经获得猪iPSC的工作基础上，通过Vc添加进而促进猪iPSC的重编程，旨在确定pre-iPSC阶段到完全重编程iPSC阶段中外源基因和内源基因甲基化的动态变化过程。进而揭示Vc介导Tet家族成员羟化5mC成为5hmC的重编程信号通路，以及Tet1和Tet2基因在两个不同的重编程阶段（中、后期重编程阶段）中iPSC诱导及iPSC多能性维持中的重要作用。

中文关键词： 维生素C；猪；诱导多潜能干细胞；重编程；

英文摘要： At present low efficiency and poor quality of iPSC is a bottleneck in their application to clinical treatment.General agreement that a major cause of low efficiency of iPSC goes through a pre-iPSC stage in somatic cell reprogramming process. Somatic cells can be fully reprogrammed only to bypass pre-iPSC stage. Histone demethylating enzymes activity of Jhdm1a and Jhdm1b are regulated to maintain Dlk1-Dio3 imprinting by Vitamin c, which contribute to iPSC completely reprogrammed state. Vc may promote the 5mC of Tet family members into 5hmC, perhaps this is a potential mechanism for somatic cell reprogramming. In this project we have already acquired the iPSC in pigs. Vc is added to promote iPSC reprogramming of pigs to identify methylation changes of exogenous and endogenous genes from pre-iPSC phase to the iPSC phase. Further the project is to reveal a signaling pathway of reprogramming that Vc mediate Tet family members that make 5mC hydroxylation into 5hmC. The project study that Tet1 and Tet2 maintain iPSC pluripotency to have an important role in two different reprogramming phases (middle and later stages of reprogramming).

英文关键词： Vitamin C；pigs；iPSC；reprogramming；