诱导多能性干细胞（iPS）是一个多步骤、低效率、长周期的过程，需要克服多个分子路障，揭示这些路障对阐明细胞命运决定分子机制及形成诱导多能性干细胞新技术具有重要意义。在前期筛选工作中，课题组首次发现过表达c-Jun几乎完全抑制体细胞重编程，而其拮抗剂则可显著提高重编程效率，甚至替代关键重编程因子。该发现表明c-Jun是体细胞重编程过程中的重要路障。本研究拟通过基因敲除、突变、过表达技术来调控c-Jun的活性和功能，并结合RNA-seq和生物信息学分析来研究c-Jun拮抗剂提高重编程效率、替代重编程因子的分子机理 ，并以此为基础建立以c-Jun拮抗剂为中心的无Yamanaka四因子（OKSM）的体细胞重编程因子组合。本研究将揭示新的重编程路障，并形成诱导多能性干细胞新技术，为理解体细胞重编程及细胞命运转变的内在分子机制提供新的思路和视角。

Somatic cell reprogramming by defined factors is a multi-step, low efficiency and time-consuming process which need overcome various molecular barriers. Revealing these barriers is important for understanding the molecular mechanisms of cell fate determination and promoting reprogramming technology. In the preliminary work ,our team discovered that c-Jun can block somatic reprogramming completely for the first time, however, its antagonists can significantly improve the reprograming efficiency and even replace the core reprogramming factors. These results suggested that c-Jun is a barrier of somatic reprogramming. In this project, We will modulate the activity and function of c-Jun by using the classic biology technologies such as gene knockout , mutation, and overexpression, combining the high-throughout RNA-seq and bioinformatics analysis, to investigate the molecular mechanisms by which c-Jun antagonists promote reprogramming efficiency and replace the classical reprogramming factors . Finally ,we will establish a non-Yamanaka reprogramming factors cocktails based on c-Jun antagonists. This project will reveal a new reprogramming barrier , improve the somatic reprogramming technology, and offer a new insight into understanding the molecular mechanisms of somatic cell reprogramming and cell fate determination.