毛乳头（DP）是毛囊中一群特化的真皮成纤维细胞，作为信号中心活化毛囊干细胞（HFSCs）从而调控毛发再生，但其介导HFSCs活化的早期信号尚不明确。我们的前期结果发现：在拔毛诱导毛囊生长期启动时，mTOR信号先在DP中迅速而短暂地激活，然后才在HFSCs中激活，且其激活时间远早于目前已知的其他信号；利用mTOR的抑制剂抑制mTOR信号能阻断HFSCs活化。由此推测：DP中的mTOR信号可能是生长期启动早期激活的信号，并在HFSCs活化中起关键作用。本课题将在前期发现的基础上，利用DP条件性敲除和药理抑制mTOR的小鼠模型，结合RNA-seq测序及常规实验手段进一步研究DP中的mTOR信号在毛发再生中的作用及其分子机制，并探讨mTOR信号在雄激素源性脱发DP和HFSCs中的变化及潜在作用。本研究将有助于揭示毛发再生中DP介导HFSCs活化的早期分子机制，为毛囊重建与临床脱发治疗提供重要线索。

Hair follicle dermal papilla (DP) cells are specialized dermal fibroblasts, acting as the signaling center for the activation of hair follicle stem cells (HFSCs) to regulate hair regeneration, but the early signals through which DP activates HFSCs remain undefined. Our previous results showed that upon plucking-induced anagen initiation, mTOR signaling was immediately but transiently activated in DP cells and then activated in HFSCs, prior to other signals activated in DP described previously. Moreover, inhibition of mTOR signaling in hair follicles by rapamycin, a specific mTOR inhibitor, could restrain the activation of HFSCs significantly. Based on this discovery, we speculate that mTOR signaling is the early signaling activated in DP at the onset of anagen during hair regeneration, which plays a key role in HFSC activation. In this project, by employing both a conditional gene targeting strategy and a pharmacological inhibition method, as well as RNA-seq analysis and regular cellular and molecular biology methods, we’ll further study the role of mTOR signaling in DP cells and its underlying mechanism for activating HFSCs during hair regeneration, and explore the mTOR signaling changes in DP and HFSCs between frontal balding and occipital non-balding areas, and its underlying role in the pathogenesis of androgenetic alopecia. Our study will not only contribute to revealing the early molecular mechanism through which DP activates HFSCs during hair regeneration, but also provide important cues for the hair follicle reconstruction and hair loss treatment.