肺脏疾病的发生发展往往与肺部支气管和肺泡等组织结构的不可逆损伤有密不可分的联系。对于肺脏的不可逆损伤，目前临床上目前并没有真正有效的治疗方法。而基于干细胞的再生医学则可能是逆转肺部损伤、恢复肺组织正常功能最大的希望所在。由此可见，成体肺脏干细胞的鉴定对于肺脏的损伤修复再生有重要的价值。本课题申请人在世界上率先完成了成体小鼠肺脏干细胞的鉴定工作（Zuo et.al.,Nature, 2015）。在本项目中，申请人将尝试对成年人体肺脏干细胞进行分离和扩增，并结合体外三维微器官培养和干细胞肺内移植等方法对肺脏干细胞的功能及相关分子机制进行深入研究。重点关注人肺脏干细胞的身份鉴定及其增殖分化过程中主要的分子调控机理，在此基础之上，重点关注如何提高人肺脏干细胞的移植和分化效率，重点关注如何构建患者个体化的人-鼠嵌合肺用于今后辅助疾病的个体化诊断及治疗。

Irreversible destruction of bronchi and alveoli can lead to multipleincurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissueis one of the biggest hopes to reverse the damage and cure such diseases. Previously we showed a rare population of lung stem cells in murine lung (Zuo et.al., Nature 2015). Here in this proposal, we plan to identify lung stem cells in human. By combining stem cell isolation/expansion, 3D organoid culture and lung stem cell transplantation technique, we will further study the stem cell properties as well as the related molecular processes. Our study will focus on how to boost the transplantation/differentiation efficiency of human lung stem cells. We also focus on the how to build the personalized human-mouse chimeric lung, which can be applied to personalized disease diagnosis and treatment in future.