Extended Data Fig. 9. Metaplastic KRT5+ basal cells and SMA+ fibroblastic foci in the alveoli of IPF lungs.

(a) UMAP projection of mesenchyme from each individual donor that was used in single cell RNA-seq analysis with contributing cell number.

(b) Expression of basal cell markers NGFR, p63, and KRT14, in KRT5+ basal cells in human IPF, along with mouse bleomycin injured lungs and murine airway progenitor-derived organoids. This experiment was repeated three times independently with similar results.

(c) Ectopic expression of KRT5 and SMA in the alveoli of IPF lungs form honeycomb cysts and fibroblast foci, respectively. This experiment was repeated independently twice with similar results.

(d) Average cell-to-cell distance shows equivalent proximity of metaplastic KRT5 and endogenous SFTPC cells to SMA+ fibroblastic foci (n = 3,280 KRT5 cells, n = 2,215 SFTPC cells; each datapoint represents an individual distance measurement with all measurements plotted for 3 samples; one-tailed unpaired Student’s t-test).

(e,f) Unsorted epithelial organoids derived from dissociated IPF lungs grew KRT5+ organoids, and BMP4 attenuated the number and size of IPF-derived organoids. (n = 5; each data point represents one well; one-tailed unpaired Student’s t-test) Data are expressed as mean ± SD. Scale bars, 100 µm.