Extended Data Fig. 8: Mapping cellular origins of lung disease by cell-selective expression of disease genes.

a, Dot plots of expression of lung disease genes (numbered, associated disease shown above) enriched in specific lung cell types (SS2 datasets). Red, novel cell type association of gene or disease; grey, diseases with developmental phenotype. AWS, Alagille–Watson syndrome; BBS, Bardet–Biedl syndrome; CF, cystic fibrosis; Dys, dysplasia; EDS, Ehlers-Danlos syndrome; Fam Med, familial Mediterranean; IPF, idiopathic pulmonary fibrosis; PH, pulmonary hypertension; SGB, Simpson-Golabi-Behmel; SM, smooth muscle; SMD, surfactant metabolism dysfunction; TB, tuberculosis; VDES, Van den Ende-Gupta syndrome. b, Dot plot of expression (SS2 dataset) of all genes implicated in pulmonary hypertension, tuberculosis and COPD or emphysema (OMIM, Mendelian disease genes from OMIM database; GWAS, genome-wide association genes ≥ 10⁻²⁰ significance). Note canonical AT2 cells (red shading) express all and AT2-signalling cells (blue shading) express most. c, smFISH of alveolar section of adult human lung probed for in pulmonary hypertension disease gene KCNK3 (red) and pericyte marker COX4I2 (white) with DAPI counterstain (blue) and ECM autoflourescence (green). Note pericyte-specific expression (arrowheads, 91% of COX4I2⁺ pericytes were KCNK3⁺, n = 77). Scale bar, 5 μm. Cell numbers for each type given in Supplementary Table 2. d, smFISH of alveolar section of adult human lung probed for atrioventricular (AV) dysplasia gene ACVRL1 (red), endothelial marker CLDN5 (white) with DAPI counterstain. Note ACVRL1 CLDN5 double-positive capillaries (white arrowheads, 70% of CLDN5⁺ capillaries were ACVRL1⁺, n = 102) and some CLDN5 single-positive capillaries (yellow arrowheads). Scale bar, 5 μm. e, smFISH of alveolar section of adult human lung probed for COPD or emphysema gene SERPINA1 and AT2 marker SFTPC, and DAPI. Note AT2-specific expression (arrowheads; 93% of AT2 cells were SERPINA1⁺, n = 176). Scale bar, 5 μm. For more details on statistics and reproducibility, see Methods.