Fig. 1: Identification of an aberrant intermediate alveolar epithelial population in the Sftpc^C121G model of pulmonary fibrosis.

a Schematic of chronic tamoxifen-induced Sftpc^C121G mutation model and subsequent cell sorting for single-cell RNA sequencing (scRNAseq). b Representative (n = 4 biological replicates) Trichrome staining with fibrosis severity scoring (normal = blue, moderate = green, and severe = red) and bar graph showing relative amounts of injury per lung lobe. c scRNAseq UMAP representation of mesenchymal, proximal (airway), and distal (alveolar) epithelial subsets in both Sftpc^WT and Sftpc^C121G mice. Inserts depict re-clustered subset analysis of distal epithelium. d Violin plots of relative gene expression in the distal epithelium comparing expression between the two genotypes. Two-way Student’s t test. p values are shown. e Cluster annotation based on marker gene expression in the alveolar epithelium. f UMAP representation of marker gene scores of distal epithelial populations. UPR, unfolded protein response. g Dot plot of individual gene expression in distal epithelial cell populations. h Gene score representation by UMAP and dot plots of signature marker genes described in murine basaloid-like cells¹⁹. i Gene score dot plots from human aberrant basaloid populations^14,16. j UMAP representation of profibrotic genes enriched within the aberrant intermediate epithelial cell population. Schematics Created in BioRender. Rodriguez, L. (2025) https://BioRender.com/19kfeg6.