Fig. 2: Injured PT cells can adopt a pro-inflammatory, pro-fibrotic phenotype.

a UMAP of proximal tubule (PT) cells coloured by cell phenotype and projected RNA velocities (arrows). b Barplot showing mean (±SEM) percentage of injured and inflammatory PT cells in control (n = 7) and obstructed (UUO, n = 5) kidneys as a proportion of total PT cells. Wilcoxon rank-sum test. c Dot plot of selected differentially expressed genes in healthy, injured and inflammatory PT cells. Dot colours show the averaged gene expression values (log scale); size indicates proportion of cells expressing each gene. d Identification of inflammatory PT cells in the Kidney Precision Medicine Project (KPMP) snRNA-seq dataset⁴. Top panel: original adaptive PT (aPT) annotations; bottom panel: KPMP cells adopting an inflammatory PT cell phenotype. e Density plot highlighting cells co-expressing injury (HAVCR1, VCAM1) and inflammatory (CCL2, CXCL1) cell specific transcripts. f Top panel: UMAP (as in Fig. 2a) with cells ordered in pseudotime on a trajectory from healthy PT segments to the inflammatory cell state. Bottom panel: percentage of cells in each subcluster as a proportion of total PT cells at that trajectory point. g Heatmap of scaled gene expression along the pseudotime trajectory. h Signature scores of GO terms enriched in healthy (PT S1-S3) or injured and inflammatory PT cells. i Proportion of total PT cells adopting a healthy, injured and inflammatory phenotype at different timepoints in single-cell/nuclei datasets in murine models of ischaemia-reperfusion injury (IRI, top⁹) and reversible unilateral ureteric obstruction (R-UUO, bottom¹⁵). j Genes differentially expressed in inflammatory PT cells in the CosMx (6000-plex panel) dataset. The dot colours show the averaged gene expression values (log scale) and size indicates proportion of cells expressing each gene. k Representative image of obstructed tissue section analysed by CosMx, with dots representing cells in their 2D coordinates. PT cells are coloured according to cell state, with selected other cell types highlighted. Plots on the right show high-resolution cell segmentation boundaries in areas enriched with inflammatory (top) or injured PT cells (bottom). Dots represent individual injury-associated (red) and inflammatory-associated (yellow) transcripts. Source data are provided as a Source Data file.