Fig. 6: Alveolar remodeling at airspace resolution.

a, Representation of lumen segmentation pipeline. b, Heatmap of predicted expression of each gene that was significantly associated with pseudotime. The top annotation shows select cell types, cell niches and transcript niches that were associated with pseudotime, with the darkest shade of each color representing the maximum proportion of that cell type or niche found across all airspaces. Disease severity is split into unaffected (blue), less affected (pink) and more affected (red). c, Scaled expression across cell types for the 124 genes with altered expression in the homeostatic (89 genes) or early remodeling stages (35 genes) from b, using only cells that were contained within one of the 1,747 airspaces. Cell-type colors are by lineage as in Fig. 2. On the top, boxes are filled in for each gene if it showed a significant change in expression in at least one cell type across the pseudotime of each of the following lineages: endothelial (orange), epithelial (green), lymphoid (purple), myeloid (pink) and mesenchymal (blue). Percentages were calculated as the number of significant tests (FDR < 0.05) in either the homeostasis (green, left) or early remodeling (yellow, right) stages that occurred across the pseudotime in all cell types of each lineage divided by the total number of significant tests for that stage of alveolar remodeling. On the y axes, z score of 0 has been marked on each plot with a dashed line. d, H&E images of mixed alveolar (FABP4⁺) and SPP1⁺ macrophage accumulations in two alveoli ranked near the end of the pseudotime trajectory, overlaid with transcript expression for all listed genes. Above the H&Es, each alveolus is marked by its position in pseudotime, and the proportion of alveolar and SPP1⁺ macrophages is shown for each airspace across pseudotime as in b. The example alveoli shown are VUILD115MA_90 (cHP diagnosis; top) and VUILD78MA_27 (IPAF, bottom). Scale bars on the bottom right of each H&E = 20 µm.