A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung [ST]. A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung [ST]

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, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatially resolved transcriptomics into a web-based, open platform for interactive exploration. We show distinct gene expression programs, 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. Overall design: One of the two lungs (preferentially the left), from each donor, was snap frozen in cryomatrix and further used for histological analyses. We cut 10-12μm-thick tissue sections with a cryostat (Leica CM3050S or analogue) and collected them onto poly-lysine coated slides (VWR Cat No. 631-0107) NOTE FROM SUBMITTER: raw reads from our cohort are considered sensate and protected by GDPR regulations, and will therefore be uploaded to Swedish federated EGA.