Fig. 5: Aberrant cellular communities observed within spatially resolved niches.
a, Comparison of aberrant cell proportions across snRNA-seq and Xenium modalities. Cell states were quantified as the fraction of each aberrant population relative to its parent lineage in both snRNA-seq and Xenium for matched participants (n = 38). Samples were ordered by the snRNA-seq-derived fraction and divided into quartiles (Q1–Q4, x axis). The y axis displays the corresponding Xenium-derived proportions for the same participants. Shown are inflamed AT2i per AT2 cells, inflamed AT1i per AT1 cells, inflamed fibroblasts (fibroi) per all fibroblasts, inflamed gCapi per gCap cells, inflamed macrophages (Mi) per macrophages, IMCHIT1 per macrophages, ABC per epithelial cells and CTHRC1+ fibroblasts per all fibroblasts. Box plots show the median, IQR and 1.5× IQR whiskers. Pairwise differences were assessed using two-sided Wilcoxon rank-sum tests with Benjamini–Hochberg correction. *FDR < 0.10, **FDR < 0.05, ***FDR < 0.01. b, Dot plot summarizing the distribution of cell types across spatially defined niches. Columns correspond to cell types and rows to niches, defined by their enriched populations—airway, large artery, low-immune parenchyma 1 and 2 (LI-parenchyma 1, LI-parenchyma 2), AM, inflamed, remodeling, CHIT1/CD4/CD8 and B cell niches. Dot size reflects the relative proportion of each cell type within each niche, and dot color indicates niche identity. c, Stacked barplots showing the proportion of cells assigned to each niche across disease severity groups, including NS/NS, GOLD stage I/II, GOLD stage III and GOLD stage IV. Colors correspond to niche identities as defined in b. d–f, Spatial localization of canonical and disease-associated cell types, cellular neighborhoods and gene expression across representative ROIs. Top, cellular niche maps based on cell-type classification and location. Each color denotes a distinct population. ROIs include (d) two distinct LI parenchymal and inflamed niches, (e) remodeling niches and (f) B cell and CHIT1/CD4/CD8 niches. Middle, cell-type overlay showing spatial proximity of cell populations. Cell types labeled by color. Bottom, spatial gene expression maps highlighting key inflammatory, remodeling and immune transcripts. Each dot represents a detected transcript labeled by color. Dot size and color density are scaled for visualization and reflect relative, not absolute transcript abundance. Scale bars = 200 μm (top), 100 μm or 50 μm (middle) and 100 μm or 50 μm (bottom).
