气管干细胞介导气管再生修复及重塑的机理研究

成体干细胞在机体受损时能够被激活，离开其所在微环境，对组织进行修复再生。果蝇的气管干细胞在特定时期能够迁移至衰退的气管处，形成新的气管系统，为研究组织器官再生提供了新模型。我们前期工作发现了成纤维细胞生长因子FGF、骨形态发生蛋白Dpp等旁分泌信号对果蝇气管发育的调控；制备了能够实时监测多条代谢通路活性的荧光探针，并观测到气管再生修复与代谢抑制的相关性。因此，本项目拟通过深入研究果蝇气管干细胞，探索干细胞激活和迁移的调控机制。建立各类气管细胞表达谱，鉴定介导气管修复重塑的气管干细胞，并揭示气管修复再生中不同类型细胞间的相互作用，阐述微环境组分对气管干细胞激活的调控机制，最终解析气管保持再生修复能力的关键机制。

Adult stem cells move out of microenvironment and contribute to tissue regeneration in response to body injury. Drosophila tracheal stem cells replenish the decaying branches and regenerate tracheal system, which provides a unique model to study organ regeneration. Our previous reports show that Fibroblast Growth Factor (FGF) and Decapentaplegic (Dpp) are required for tracheogenesis. We generated various biosensors for tracking the activity of multiple metabolic pathways. Furthermore, we observed a correlation between metabolic depression and tracheal regeneration. Present project will investigate the mechanism that governs activation and migration of tracheal stem cells, establish the expression atlas of Drosophila trachea, identify the molecular signature of tracheal stem cells, reveal cell-cell communication during tracheal regeneration, elucidate the biological function of microenvironment in activation of tracheal stem cells, and illustrate molecular details underlying tracheal regeneration capability.