2013年，本实验室首次利用小分子化合物组合将小鼠体细胞重编程为诱导多潜能干细胞（Chemically-induced pluripotent stem cells, CiPSCs），建立了一条全新的实现体细胞重编程的途径。化学小分子具有非整合、操作简单、时空调控性强、作用可逆等诸多不可替代的优势，CiPS技术有可能成为新的下一代体细胞重编程技术。本项目将从以下三个方面对CiPS细胞的诱导过程进行深入研究：1）分析CiPS细胞诱导过程中的分子机理，绘制分子路径图谱，比较与传统转录因子重编程过程的异同；2）研究CiPS细胞诱导过程中组蛋白修饰和DNA甲基化的动态变化，描绘表观遗传变化图谱；3）研究CiPS诱导过程中关键小分子启动干性基因的分子机理。本研究将有望揭示新的体细胞重编程机制，为体外获得多潜能干细胞提供新的思路和途径，并从新的视角理解细胞命运是如何决定和转变的。

We developed a novel strategy that can robustly reprogram adult somatic cells into the pluripotent state using only a chemical cocktail, a procedure that is termed “chemical reprogramming” (Science, 2013, 341:651-654; Cell, 2015, 163:1678-1691). This study provides an important proof-of-principle demonstration that the manipulation of signaling pathways and epigenetic regulators alone is sufficient to endow cells with pluripotency and generate CiPSCs (Chemically-induced pluripotent stem cells). In this study, we will focus our research on the following three respects: 1) To further explore the underlying mechanism, and draw a molecular roadmap during chemical reprogramming; 2) To analyze the dynamics of histone modification and DNA methylation during chemical reprogramming, and describe the epigenetic roadmap; 3) To study the molecular mechanism to activate pluripotency genes by the key small molecules. This work should help better understand cell fate determination, improve the CiPS induction efficiency, and develop novel methods for CiPS induction.