组织工程膀胱对于解决临床膀胱再生重建难题具有重要意义，获取足量的平滑肌种子细胞是组织工程膀胱的关键技术环节。干细胞的命运决定与细胞外基质力学信号密切相关。在前个项目（81470926）中，我们发现膀胱脱细胞基质（BAM）能促进尿源干细胞（USCs）向平滑肌细胞分化，并激活MAPK信号通路的ERK、p38，但具体分子机制尚不清楚。前期研究发现BAM基质的力学信号促进YAP/TAZ入核，启动USCs向平滑肌细胞分化；此过程中，力学敏感性离子通道Piezo1活化，激活MAPK信号通路，该信号通路是调控YAP/TAZ的上游机制。据此我们提出假说，在BAM材料力学信号刺激下，USCs细胞膜上Piezo1感知此力学信号，活化MAPK信号通路，促进力学传感器YAP/TAZ入核，结合转录因子，启动平滑肌分化。本项目拟探索提高USCs向平滑肌细胞分化效率的分子机制，同时为其在组织工程膀胱的应用提供理论依据。

Tissue engineering bladder is of great significance to solve the difficult problem of clinical bladder reconstruction. Obtaining sufficient smooth muscle seed cells is the key technical issues of tissue engineering bladder. The fate of stem cells is closely related to the mechanical signals of extracellular matrix. In the previous project (81470926), we found that bladder acellular matrix (BAM) could promote the differentiation of urine-derived stem cells (USCs) into smooth muscle cells and activate ERK and p38 of MAPK signaling pathway, but the specific molecular mechanism was still unclear. Previous studies have found that the mechanical signals of BAM matrix promote YAP/TAZ nucleus entry and initiate USCs differentiation into smooth muscle cells. In this process, the mechanically sensitive ion channel Piezo1 is activated, activating the MAPK signal pathway, which is the upstream mechanism for regulating YAP/TAZ.According to this, we propose a hypothesis that under the stimulation of BAM material mechanical signal, Piezo1 on USCs cell membrane senses this mechanical signal, activates MAPK signal pathway, promotes YAP/TAZ nuclear entry, and starts smooth muscle differentiation pathway in combination with transcription factors. This project intends to explore the molecular mechanism of improving the differentiation efficiency of USCs into smooth muscle and provide theoretical basis for its application in tissue engineering bladder.