Sox2通过Wnt和TGF-β/BMP双通路介导皮肤前体细胞调控毛囊生长的机制研究

脱发是皮肤科最常见疾病之一，在人群中患病率高。目前，脱发治疗仍缺乏有效手段。皮肤前体细胞（SKP）是从真皮毛乳头中分离的有自我更新和多向分化潜能的干细胞，转培养法获得SKP（tSKP）与传统SKP具有相似的生物学特性。Sox2阳性毛乳头来源SKP具有毛囊调控作用，但具体机制尚不清楚。Sox2是SKP经典标志物，主要调控干细胞发育和分化，也是毛囊调控的重要因子。Wnt和TGF-β/BMP通路在毛囊调控中共同发挥作用。前期研究中，我们对SKP测序发现Wnt及TGF-β/BMP通路因子表达，推测其对毛囊调控通过双通路互作实现，该作用由Sox2介导。本研究拟通过单细胞测序、流式细胞分选、毛囊周期和毛发重建模型构建等技术，以Sox2+tSKP为干预措施，从分子、细胞和动物模型三个层面探讨其对毛囊调控的具体机制，为开发防止脱发药物提供新靶点。

Alopecia is one of the most common skin disorders among general population, with a high prevalence. Treatment options for alopecia have limited success. Skin-derived precursors (SKP), isolated from dermal papilla (DP), are stem cells with self-renewal and multi-lineage differentiation capacity. SKP trans-cultured from monolayer fibroblast culture (henceforth termed tSKP) are morphologically and functionally similar to traditional SKP. Recent study showed that SKP derived from DP expression of Sox2 regulated hair follicle growth. However, the underlying mechanism is currently largely unknown. The transcription factor Sox2 is a crucial marker of SKP, which regulating cell growth and differentiation in stem cells, and it is also a key factor in hair development. Both Wnt and transforming growth factor-β(TGF-β)/ bone morphogenic protein (BMP) signaling pathways are involved in the formation and growth of hair follicle. Current studies showed that the crosstalk between Wnt and TGF-β/BMP pathways within DP played an important role in regulating hair growth. In previous study, we performed RNA-sequence to investigate RNA profiles in SKP and found SKP expressed multiple genes related to Wnt and TGF-β/BMP pathways. Therefore, we speculate SKP regulate hair follicle growth through Wnt and TGF-β/BMP signaling interaction, which is mediated by Sox2-positive spheres. In this study, we intent to use technique of single-cell sequence, flow cytometry, and establish hair cycle model and Patch Assay model, to figure out the molecular mechanisms of Sox2-postive tSKP in regulating hair follicle growth and to provide new targets for preventing and treating hair loss.