DOC-1R在小鼠胚胎干细胞多能性维持过程中发挥着重要作用，但其机制尚不明确。我们发现，DOC-1R能够通过Wnt/β-catenin信号通路调节胚胎干细胞增殖与分化的重要因子CDK2的表达及活性，结合现有文献我们推测，DOC-1R可能负性调节人胚胎干细胞增殖过程，同时DOC-1R过表达与低表达能够影响胚胎干细胞向不同方向进行分化,Wnt/β-catenin/CDK2信号途径可能介导上述过程的发生。本项目拟采用体外与体内实验方法，确定DOC-1R过表达及沉默对人胚胎干细胞增殖分化过程的影响，阐明DOC-1R介导Wnt/β-catenin/CDK2途径参与人胚胎干细胞增殖分化的分子机制及分子靶点，深入探讨DOC-1R在人胚胎干细胞增殖分化过程中的生物学作用。本项目的完成将有助于阐明DOC-1R在哺乳动物胚胎早期发育过程中的作用，为人胚胎干细胞自我更新的维护及定向诱导等相关机理的理解开辟思路。

DOC-1R is an essential regulator for maintaining pluripotency in mouse embryonic stem cells,but its mechanisms remained undetectable. Previously we demonstrated that DOC-1R could repress the expression and activity of CDK2, the important modulator in proliferation and differentiation of embryonic stem cells, through Wnt/β-catenin signaling pathway, suggesting that DOC-1R might negatively regulate the proliferation of human embryonic stem cells as well as induce its differentiation via Wnt/β-catenin/CDK2 signaling transduction. In this project, we would investigate the effects of DOC-1R in the proliferation and differentiation of human embryonic stem cells by overexpressing and silencing DOC-1R expression and clarify its potential mechanisms mediating by Wnt/β-catenin/CDK2 signaling transduction, in vitro and in vivo. Moreover, we will determine the target(s) of DOC-1R in Wnt/β-catenin/CDK2 signaling transduction and demonstrate how the regulation happens. The results of this project will be helpful to elucidate the biological roles of DOC-1R in stem cells as well as provide data for understanding early embryonic development in vertebrates and induced differentiation of stem cells.