目前，针对维生素C促进体细胞重编程的研究主要集中在细胞内外抗坏血酸浓度的提高对下游表观遗传修饰的影响。前期研究中发现：维生素C的代谢中间产物脱氢抗坏血酸（DHA）也可以显著促进体细胞重编程。由于在水相中的快速降解，DHA难以通过再次还原为抗坏血酸的途径促进重编程。因此，维生素C对体细胞重编程的部分促进作用可能是通过DHA或者其他代谢产物实现的。本项目计划首先确定DHA以及其他形式的维生素C（如抗坏血酸-2-磷酸三钠盐等）对培养基以及细胞内抗坏血酸浓度的调控作用。在进一步确定维生素C的主要代谢产物（如：2,3-二酮-L-古洛糖酸盐、苏糖酸盐、赤藓酮糖、草酸盐等）对体细胞重编程的具体调控作用，同时结合转录组测序、DNA和组蛋白甲基化分析等技术手段揭示相关的调控机制。本项目的研究有助于进一步揭示体细胞重编程的相关机制，推动以干细胞为基础的再生医学发展，也将为维生素C的相关研究提供新的切入点。

Vitamin C increases the efficiency of induced pluripotent stem cells (iPSCs) generation and the quality of the generated cells. However, the intermediate metabolite, dehydroascorbic acid (DHA), of vitamin C also promotes the reprogramming from somatic cells. Considering the rapid degradation of DHA in aqueous phase, the beneficial roles of DHA to somatic reprogramming would not be due to the ascorbic acid reduced again from DHA. Thus we hypothesized that, vitamin C might facilitate the reprogramming via its metabolites at least partially. In the current studies, we will first determine the concentration of ascorbic acid in culture medium and intracellular after incubating cells with DHA or other forms of vitamin C like ascorbic acid-2-phosphate. Then we will determine the beneficial roles played by solutions with ascorbic acid or DHA at different metabolic stages in inducing iPSCs. The effects of the main metabolites of vitamin C like, 2,3-diketogulonate, threonate, erythrulose, and oxalate, on reprogramming were then determined individually. The related mechanisms would be revealed by employing RNA-seq or DNA/histone methylation detection. The current results should not only provide further information of reprogramming and facilitate the clinic application of regeneration medicine, but also extend our understanding on vitamin C.