诱导多潜能干（iPS）细胞的出现规避了胚胎干细胞的免疫原性和伦理学问题，从而为其在再生医学方面的应用开辟了新道路。但在iPS细胞应用前必须解决其诱导效率低和致瘤性问题。研究证明，细胞重编程与DNA甲基化有关，去甲基化可能提高iPS细胞的诱导效率。叶酸通过提供或接受一碳单位参与DNA的甲基化过程，当细胞无叶酸时可引起基因组的低甲基化；我们的预实验结果显示叶酸缺乏可使靶细胞Oct4和Nanog启动子部分区域去甲基化，原癌基因c-Myc表达增高，抑癌基因p53表达降低。故本研究试图通过对靶细胞进行控制性叶酸剥夺，在可能提高iPS细胞诱导效率的同时，还可能替代部分外源性转录因子降低致瘤性；并通过U0126替代叶酸缺乏条件，丰富iPS细胞诱导机制。最终试图通过对靶细胞进行可控性的叶酸剥夺，逐步实现完全利用小分子化合物诱导iPS细胞，为细胞治疗提供足量、安全的细胞，为其理论研究和转化应用的探索提供平台

Induced pluripotent stem (iPS)cells pave a way in regenenrative medicine for evading the ethical and immunological incompatibility issues of embryonic stem cells.The remaining technical barriers in the reprogramming process are the inefficiency and tumorigenicity.It has proved that cell reprogramming is corrate with DNA methylation ,which is demethylation could improve the induced efficiency of iPS cells.Folate participate in DNA methylation by providing or accepting onecarbon unit, folate-deprived could induce DNA demethylation, and our experimental results also show that mouse embryonic fibroblasts were cultured in non-folate condition,the promoter region of Oct4 and Nanog demethylated partly,c-Myc increased expression and P53 decreased. As a result, we'd like to controlled deprive folate in cell culturing, maybe improve the inducing efficiency,and also decrease the number of transcription factors to reduce the tumorigenicity；at the same time,we will instead lack-folate by U0126,a MAPK signal inhibitor,to explore the mechanism of cell reprogramming. And the ultimate purpose is that inducing iPS cells by the pure small-molecule chemicals gradually,providing enough safer iPS cells for cell therapy,and bringing out a platform for studying its' mechanism and exploring the application in translational medicine.