我们提供了一个深入的单细胞地图，突显了来自27名供体的正常和疾病肺部衍生的体外多培养系统上的人类原位气道上皮。我们的大规模单细胞分析技术鉴定出了人类远端肺中罕见气道上皮细胞类型的新细胞状态和分化轨迹。通过整合人类肺组织的单细胞数据集，我们发现了免疫激活亚群，在来自慢性呼吸系统疾病患者的肺部和器官样体中富集。为了展示我们平台的全部潜力，我们进一步研究了体外气道模型中不同呼吸道病毒感染的转录组反应。我们的工作为研究人类原位肺细胞在体外的细胞和分子特征以及它们与体内人类组织的相关性提供了单细胞的指导路线。© 2023. 作者。

We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.© 2023. The Author(s).