Fig. 3 |. Impaired lung regeneration and sources of inflammation.

a, b, UMAP of investigated alveolar and airway epithelial cells (a) and corresponding group assignments (b). c, Differential gene expression (log-normalized, scaled; see Methods) of AT1 and AT2 cells from COVID-19 and control lungs. Columns, single cells; rows, expression of top-regulated genes. Left bar, lineage markers for AT1 (purple) and AT2 (pink) cells. Colour-coded top lanes indicate expression strength of signatures (log-normalized; see Methods) and group assignment as indicated on the right. exp., expression. d, e, Violin plots of ETV5 and CAV1 mRNA expression (log-normalized) in AT2 and AT1 cells, respectively; Wilcoxon signed-rank test with Bonferroni correction. f, UMAP embedding of AT1 and AT2 cells and identified DATPs; insert indicates group assignments. g, Violin plots of DATP signature expression (log-normalized) in AT1 and AT2 cells. Wilcoxon singed-rank test. h, First three DCs showing main trajectories of AT2 and AT1 cells and DATPs, expression of DATP signature and group assignment (insert). i, Fractions of DATP and AT cells in control (n = 7) and COVID-19 lungs (n = 19). Middle line, median; box edges, 25th and 75th percentiles; whiskers, most extreme points that do not exceed ±1.5 × IQR. Wilcoxon rank-sum test. j, Representative immunofluorescence staining for pro-SPC, KRT8 and DAPI in control and COVID-19 lung tissue; top, representative area with overlay; bottom, small images with individual channels of selected area. Scale bar, 50 μm. k, l, Tissue mass cytometric quantification of IL-1β (k) and IL-6 (l) in healthy lung tissue and samples from donors with different infectious aetiologies. Each dot represents quantification of IL-1β and IL-6 in a region of interest (ROI); two-sided Mann–Whitney test with Benjamini–Hochberg false discovery rate (FDR) adjustment.