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. 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.