The lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a comprehensive topographic atlas of early human lung development. Here we report 83 cell states and several spatially resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated single-cell RNA sequencing and spatially resolved transcriptomics into a web-based, open platform for interactive exploration. We show distinct gene expression programmes, accompanying sequential events of cell differentiation and maturation of the secretory and neuroendocrine cell types in proximal epithelium. We define the origin of airway fibroblasts associated with airway smooth muscle in bronchovascular bundles and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

肺含有许多特殊的细胞类型，在组织功能和完整性中具有不同的作用。为了阐明细胞异质性的起源和机制，我们创建了早期人类肺部发育的综合地形图谱。在这里，我们报告了 83 种细胞状态和几个空间分辨的发育轨迹，并预测了定义的组织生态位内的细胞相互作用。我们将单细胞 RNA 测序和空间分辨转录组学集成到一个基于网络的开放平台中，​​用于交互式探索。我们展示了不同的基因表达程序，伴随着近端上皮中分泌细胞和神经内分泌细胞类型的细胞分化和成熟的连续事件。我们定义了与支气管血管束中气道平滑肌相关的气道成纤维细胞的起源，并描述了雪旺细胞祖细胞到控制支气管收缩的内在副交感神经元的轨迹。我们的图谱为进一步研究提供了丰富的资源，并为定义导致肺部疾病的稳态和修复机制的偏差提供了参考。