毛囊干细胞（HFSCs）迁移障碍会导致脱发、新生物形成等疾病，但其迁移调控机制不清。本项目在青年基金研究发现Wnt1促进黑色素干细胞的迁移的基础上，对Wnt1诱导HFSCs迁移的作用及其机制进行深入研究。本项目拟首先建立转基因小鼠的HFSCs示踪实验模型，并通过划痕实验、Transwell实验、细胞微图案培养实验、体视显微镜观察、双光子显微镜观察等方法分别从细胞水平、器官水平、在体水平，从正向和反向证明Wnt1调控HFSCs的迁移；然后通过条件敲除及回补实验证明E-cadherin抑制HFSCs的迁移；在此基础上，通过免疫荧光、超高分辨率显微镜观察、免疫共沉淀等方法进一步研究Wnt1调控HFSCs迁移的分子机制是通过经典Wnt信号通路负向调控E-cadherin/ß-catenin复合物的形成。本研究将延伸HFSCs两步活化机制，并能为HFSCs迁移障碍相关疾病治疗提供新的靶点。

Dysfunction of the migration of hair follicle stem cells (HFSCs)will lead to hair loss, formation of neoplasm. The mechanisms under the regulation of HFSCs migration remain unclear. Previously we found that Wnt1 could promote the migration of melanocyte stem cells. Based on that, this project will research on the roles of Wnt1 in the initiation of HFSC migration, and the mechanisms under the process. At first, this project will establish a HFSCs tracing model based on transgenetic mice. Then, this project will prove that HFSCs are regulated byboth Wnt1 and E-cadherin, from cell level, oragan level, and in vivo level. Methods and techniquesincluding wound healing assay, Transwell assay, micropattern cell culture, stereomicroscope, and two-photon microscope will be used. After that, this project will research on the molecular mechanisms during the migration of HFSCs initiated by Wnt1. We will prove the hypothesis that Wnt1 negatively regulate the formation of E-cadherin/ß-catenin complex, by using of immunofluorescence, ultra high resolution microscopy, and co-immunoprecipitiation. This project will extend the two-step mechanism of HFSCs activation, and provide new therapy targets for diseases associated with dysfunction of the migration of HFSCs.