肝干细胞具有自我复制和双向分化潜能，但其分子调控机制远未研究清楚。申请人发现KCTD10抑制肝干细胞标记基因的表达和自我更新特性，与调控干细胞的形成与分化的Notch信号通路中的受体Notch1相互作用，在KCTD10敲除小鼠模型中检测出Notch信号通路被激活，申请人据此推测KCTD10通过调控Notch信号通路影响肝干细胞的形成和分化。本项目拟通过KCTD10肝脏特异性敲除小鼠模型结合体外细胞培养及分子生物学实验，分析KCTD10对肝干细胞形成与分化的作用，研究KCTD10通过Notch信号通路调控肝干细胞形成与分化的分子机制。本项目研究结果将为进一步研发应用肝干细胞治疗临床肝脏相关疾病提供科学依据。

Liver Stem cells have the ability of self-renewal and bidirectional differentiation potential, but the molecular mechanisms involved have never been reported. The applicant found the KCTD10 inhibits the expression of the marker gene and the characterize of self-renewal in liver stem cells, and interacts with Notch1 which is a receptor of Notch signaling that decides the formation and differentiation fate of liver stem cells. Furthermore, the Notch signaling is activated in KCTD10 knockout mice. We suppose KCTD10 affects the formation and differentiation of liver stem cell by modulating Notch signaling. This project aims to study the functions of KCTD10 in the formation and differentiation of liver stem cells, and explore the molecular mechanisms involved by construction of KCTD10 liver specific knockout mice, combined with cell and molecular biology methods in vitro. The complete of this research will provide more scientific basis for further research and application of hepatic stem cells to the clinical treatment of liver diseases.