牙髓干细胞（dental pulp stem cells，DPSCs）受外界刺激时能向成牙本质向分化，形成修复性牙本质。DNA甲基化/去甲基化是重要的表观遗传修饰形式，可调控多种组织发育及细胞分化，但其对DPSCs分化的影响尚未知。本课题组前期研究表明，DNA去甲基化酶TET1（Ten-Eleven-Translocation 1）可促进牙髓细胞成牙本质分化；通过DNA甲基化芯片筛选出细胞成牙本质分化过程中甲基化水平下调的Family with sequence similarity 20 C（FAM20C）。为探索TET1能否通过调控FAM20C的甲基化水平促进DPSCs成牙本质分化，本项目拟构建TET1及FAM20C过表达、沉默DPSCs模型，研究二者对DPSCs分化性能的影响，同时阐明TET1通过何种机制调控FAM20C甲基化。本项目可望从表观遗传学角度为牙髓修复再生研究提供新思路。

Human dental pulp stem cells (DPSCs) possess the capacity to differentiate into odontoblast-like cells in respond to exogenous stimuli and play an important role in reparative dentinogenesis. DNA demethylation is a crucial epigenetic modification which regulates the proliferation and differentiation of several cell types; however, its role in the odontogenic differentiation of DPSCs is still unknown. Ten-eleven translocation 1 (TET1) is a recently discovered DNA methyldioxygenase that plays important roles in promoting DNA demethylation and transcriptional regulation. Our previous study demonstrated that TET1 could enhance the capability of odontogenic differentiation of dental pulp cells. The genome-wide DNA methylation changes of dental pulp cells were explored and family with sequence similarity 20 C (FAM20C) was found to show a significant decrease in local DNA methylation during the odontogenic differentiation. Our preliminary experiments also indicated that FAM20C expression increased during the odontogenic induction of the cells. Accordingly, we hypothesize that TET1 enhances the odontogenic differentiation of DPSCs by regulating the DNA methylation status of FAM20C. This project will firstly explore the effects of TET1 and FAM20C on the physiological properties of DPSCs following overexpression and knockdown of these genes. The research then investigates the potential mechanism of TET1-dependent DNA demethylation of FAM20C and its effect on the odontogenic differentiation of the cells. Finally, the dentinogenesis experiment in vivo will be performed to demonstrate the capacity of dental pulp repair by TET1 or FAM20C modified DPSCs. This project may illuminate the regulatory effect of TET1-dependent DNA demethylation on the odontogenic differentiation of DPSCs and may open new avenues for research into dental pulp repair and regeneration.