脱发和皮肤创伤等临床常见疾病与毛囊干细胞的状态密不可分。寻找毛囊干细胞静态维持、激活及再生的调控因子及其调控机制是解决以上问题的关键！我们发现在毛囊中特异敲除Foxp1和Foxp4转录因子，导致小鼠周期性脱发，同时毛囊干细胞被提前激活，随后逐渐消失。有意思的是，毛囊干细胞在毛囊次级生长中心再生，支持毛发继续循环，初步发现Notch信号可能参与了再生过程。本研究利用流式细胞术分选毛囊干细胞进行RNA-Seq，结合体外基因表达调控、Co-IP、ChIP及表型挽救实验等，分析Foxp1/Foxp4协同调控毛囊干细胞激活与再生的分子机制；应用皮肤重建、细胞追踪及活体成像技术实时跟踪毛囊干细胞的迁移、凋亡及再生等动态变化。本研究有助于理解Foxp1/Foxp4对毛囊干细胞命运的协同调控作用，阐明毛囊干细胞再生的分子机制，对于成体干细胞研究具有重要理论意义，对脱发治疗和皮肤创伤修复具有重要应用价值。

Severe hair loss and skin wound healing are closely associated with hair follicle stem cells (HFSCs) clinically. Exploiting the regulators and mechanism by which regulate HFSCs quiescence maintaining, activation and regeneration is critical for curing such diseases. It was found in earlier studies that the mice would be suffered from cycling hair loss when Foxp1 and Foxp4 transcription factors were conditionally knocked out in hair follcile by using K14-Cre. Moreover, HFSCs in such mutant would become precocious and hyper proliferative, then gradually fade, indicating that Foxp1 and Foxp4 play an important role in HFSCs quiescence maintaining. What’s more intriguing is that HFSCs can be regenerated in hair germ during telogen-anagen transition, and then prompt hair follicles to enter the next hair cycle. Preliminary results indicated that Notch signaling may be involved in HFSCs regeneration. In this study, we first plan to use fluorescence-activated cell sorting (FACS) to purify HFSCs for RNA-Seq analysis, combining with in vitro luciferase reporter assay, Co-IP, ChIP, and rescue assay to elaborate the underlying mechanism of Foxp1/Foxp4 synergistically regulating HFSCs; Simultaneously, Brdu pulse-chase, live imaging assay, and chamber assay would be used to track the proliferation, migration, apoptosis, regeneration, and homing status of HFSCs in vivo, and further to explore the molecular mechanism of HFSCs reprogramming and regeneration in response to Foxp1/Foxp4 deletion. Taken together, our study would favor the understanding of the role of Foxp1/Foxp4 for HFSCs fate decision and the specification of new HFSCs during hair cycle, and also provide some novel theoretical insights for adult stem cells study and clinical insights for hair loss and wound healing.