Fig. 6. Characterization of lung epithelial cells in the SfSRC mouse model.

a Schematic of Sftpc-CreER, Scgb1a1-CreER, Rosa26R-DTA, and CycB1-GFP transgenes in SfSRC mice. b IF staining of SfSRC mouse lungs with Cyp2f2 (white; club cells), Lamp3 (red; AT2 cells), CycB1-GFP (green; dividing cells) and DAPI (blue; nuclei), on days 0, 2, 3, 14, 28 and 56 after tamoxifen injection. Aw: airway. Scale bar: 100 µm. Images are representative of three independent experiments with n = 3 animals analyzed per timepoint. c Scheme of cell sorting and scRNA-seq strategy. Created with BioRender.com. d UMAP embedding showing cell type assignment of epithelial cells before (day 0, n = 5 mice), and two (n = 9 mice) and three days (n = 6 mice) after tamoxifen injection. At day 2, basal_Krt13⁺ and club_Krt15⁺ cells are highlighted. e Dot plot showing normalized enrichment score (NES) and significance for published signatures of epithelial cell types in all SfSRC mouse epithelial populations (fgsea package⁹¹, all timepoints merged). DATP damage-associated transient progenitors, PATS pre-alveolar type-1 transitional cell state, RAS respiratory airway secretory, BC basal cell, TRB-SC terminal and respiratory bronchioles secretory cell, pre-TB-SC pre-terminal bronchiole secretory cell, AEP alveolar epithelial progenitor, BASC bronchioalveolar stem cell. Cell types described in the human lung are depicted in red. f Heatmap of the top 20 marker genes for basal_Krt13⁺ and club_Krt15⁺ cells, and expression of Krt15, Krt13, and Krt4, in basal and club cells of SfSRC mice (roc test, all three timepoints merged).