神经源性SHH经由外泌体靶向递送调控毛囊干细胞的机制研究

The stem cell microenvironment plays a crucial role in the maintenance and function of stem cells. The neural microenvironment of hair follicle stem cells transmits DRG-derived SHH signals, supports hair follicle stem cell self-renewal and participates in hair follicle regeneration and peripheral epidermal damage repair, but the cellular communication mechanism between the neural microenvironment and hair follicle stem cells is not clear. SHH is secreted on extracelluar vesicles to perform its biological functions. While exosome is one of the important types of extracelluar vesicles, our preliminary data showed that mouse DRG neurons can secrete exosomes containing SHH. Therefore, we propose that neurogenic SHH functions from the end of the nerve to the recipient hair follicle stem cells through exocytosis. In this project, we intend to further characterize the exosomes secreted from DRG neurons, reveal the roles of SHH-containing exosomes in the function of hair follicle stem cells, and elucidate the communication mechanism between neuromicroenvironment and hair follicle stem cells. We will further explore the effects of neurotoxin BtxA on the secretion of neuronal exosomes and the function of hair follicle stem cells. The purpose of study is to broaden our knowledge of the function and molecular mechanism of the neuromicroenvironment by revealing the communication mechanism between the neuromicroenvironment and the recipient cells.

干细胞微环境对干细胞的维持和功能有至关重要的作用，毛囊干细胞的正常功能依赖于神经微环境的精确调节。背根神经节（DRG）神经元来源的SHH支持毛囊干细胞自我更新、参与毛囊再生和表皮损伤修复，但是SHH是如何由神经微环境到达毛囊干细胞并不清楚。作为细胞间信号分子，SHH需经特定的分泌机制到胞外发挥功能，而外泌体是神经元与周围细胞进行通讯的重要途径。预实验确认了小鼠DRG神经元在体外可以分泌包含有SHH的外泌体，由此提出神经源性SHH从神经末梢通过外泌体到达受体细胞而发挥功能的作用机制。本项目拟对DRG神经元所分泌外泌体特征进行进一步鉴定，并在体外确认外泌体SHH对毛囊干细胞的作用，从而阐明神经微环境和毛囊干细胞之间的通讯机制；并将探索神经毒素BtxA对神经元外泌体分泌的影响及对毛囊干细胞功能调控的机制。本研究将揭示神经微环境和受体细胞之间的通讯机制，增进对神经微环境的功能和作用机制的了解。

干细胞微环境对干细胞的维持和功能有至关重要的作用，毛囊干细胞的正常功能依赖于神经微环境的精确调节。背根神经节（DRG）神经元来源的SHH支持毛囊干细胞自我更新、参与毛囊再生和表皮损伤修复，但是SHH是如何由神经微环境到达毛囊干细胞并不清楚。作为细胞间信号分子，SHH需经特定的分泌机制到胞外发挥功能，而外泌体是神经元与周围细胞进行通讯的重要途径。本研究发现小鼠DRG神经元在体外可以分泌包含有SHH的外泌体，并通过BTXA干预外泌体的释放，促进了毛囊的再生，同时还发现BTXA可以促进皮肤伤口愈合。本研究揭示了神经源性因子从神经末梢通过外泌体作用于毛囊干细胞细胞而发挥功能，增进了对神经微环境的功能和作用机制的了解。