A single-cell atlas of mouse lung development

Lung organogenesis requires precise timing and coordination to effect spatial organization and function of the parenchymal cells. To provide a systematic broad-based view of the mechanisms governing the dynamic alterations in parenchymal cells over crucial periods of development, we performed a single-cell RNA-sequencing time-series yielding 102,571 epithelial, endothelial and mesenchymal cells across nine time points from embryonic day 12 to postnatal day 14 in mice. Combining computational fate-likelihood prediction with RNA in situ hybridization and immunofluorescence, we explore lineage relationships during the saccular to alveolar stage transition. The utility of this publicly searchable atlas resource (www.sucrelab.org/lungcells) is exemplified by discoveries of the complexity of type 1 pneumocyte function and characterization of mesenchymal Wnt expression patterns during the saccular and alveolar stages - wherein major expansion of the gas-exchange surface occurs. We provide an integrated view of cellular dynamics in epithelial, endothelial and mesenchymal cell populations during lung organogenesis.

Automated summary

This study used single-cell RNA sequencing to explore the dynamic alterations in parenchymal cells during lung organogenesis in mice. The research revealed lineage relationships of epithelial, endothelial, and mesenchymal cells at different developmental stages, providing a comprehensive view of cellular dynamics in lung organogenesis. The findings highlighted the complexity of type 1 pneumocyte function and characterized the expression patterns of mesenchymal Wnt during crucial stages of lung development.