脂肪酸代谢调节重编程的研究

项目名称： 脂肪酸代谢调节重编程的研究

项目编号： No.31301217

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 林兆宇

作者单位： 南京大学

项目金额： 23万元

中文摘要： 实现安全高效重编程是诱导性多能干细胞（iPSCs）研究的核心问题。本项目旨在分析重编程过程中细胞代谢途径的转换这一个关键步骤，并探讨能否通过主动增强代谢途径的变化来提高重编程效率。目前国际上iPSCs重编程过程中的代谢研究工作主要集中在糖代谢上，而较少涉及脂代谢。本项目在前期研究工作中发现脂肪酸代谢相关基因的表达量发生了改变，且该过程关键基因（肉毒碱棕榈酰基转移酶）的代谢产物能够促进重编程。这暗示脂肪酸代谢是代谢途径重编程的一个重要组成部分和效率决定因素。本项目将系统分析脂肪酸代谢在重编程过程中的作用，揭示其机制，并寻找能调控重编程效率的相关基因和小分子代谢产物。

中文关键词： 重编程；Cpt1b；软脂酰肉毒碱；氧化磷酸化；蛋白激酶C

英文摘要： The primary problem in induced pluripotetent stem cell (iPSCs) field is how to reprogram safely and efficiently. The aim of this project is to analyze the roles of cell metabolic pathway modifications in reprogramming process and determine whether the enhancement of these modifications can increase reprogramming efficiency. The research works about metabolism in iPSCs reprogramming field mainly focus on glucose, and few of them mention fatty acid. However, in the preliminary data, we found that the expression of fatty acid metabolism associated genes are significantly changed in reprogramming process. Furthermore, the metablites generated by a key enzyme (carnitine palmitoyltransferase) can promote reprogramming. It implies that fatty acid metabolism is a important component and rate-limiting factor in reprogramming process. In this project, we will analyze the mechanism underlying fatty acid metabolism in reprogramming process, find the associated genes and the small molecular metabolites which can affect reprogramming efficiency.

英文关键词： Reprogramming；Cpt1b；Palmitoylcarnitine；Oxidative phosphorylation；Protein Kinase C