Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the epithelium in response to injuries. Here, we review the key points of lung development, homeostasis and epithelial cell plasticity in response to injury and disease, because this knowledge is required to develop new lung disease treatments. Of note, canonical signaling pathways that are essential for proper lung development during embryogenesis are also involved in the pathophysiology of most chronic airway diseases. Moreover, the perfect control of these interconnected pathways is needed for the successful differentiation of induced pluripotent stem cells (iPSC) into lung cells. Indeed, differentiation of iPSC into airway epithelium and alveoli is based on the use of biomimetics of normal embryonic and fetal lung development. In vitro iPSC-based models of lung diseases can help us to better understand the impaired lung repair capacity and to identify new therapeutic targets and new approaches, such as lung cell therapy.

肺部具有复杂的结构，由不同的细胞类型组成，形成大约1700万个输气细支气管的气道分支，与5亿个气体交换肺泡相连。气道和肺泡被上皮细胞排列着，这些细胞在稳态下显示出较低的周转率，但可以响应损伤而再生上皮。在这里，我们回顾了针对损伤和疾病的肺发育，体内稳态和上皮细胞可塑性的关键点，因为开发新的肺疾病治疗需要这些知识。值得注意的是，在胚胎发生过程中正常肺发育必不可少的规范信号通路也参与了大多数慢性气道疾病的病理生理。而且，要成功地将诱导多能干细胞（iPSC）分化为肺细胞，需要对这些相互连接的路径进行完美控制。实际上，iPSC向气道上皮和肺泡的分化是基于正常胚胎和胎儿肺发育的仿生技术的使用。基于体外iPSC的肺部疾病模型可以帮助我们更好地了解受损的肺修复能力，并确定新的治疗靶点和新方法，例如肺细胞治疗。