Transcriptional profile of FRC from PP during chronic inflammatory disease. (A) UMAP showing the bioinformatically isolated 8,200 GALT FRC derived from PP of seven independently processed donors with CRC and five with CD. The colored dots depict CRC donor-derived cells included in the ileal GALT dataset (Fig. 3); the gray cells depict the added PP-derived cells from two additional CRC and five CD donors. (B) Volcano plot showing the number of significantly up- and downregulated DEG among TRC from three inflamed donors with CD and seven non-inflamed donors with CRC, based on pseudobulk analysis using all samples with >30 TRC. Line marks FAP. (C) GO-term analysis based on the same samples than in A and B. (D) Overlay of an inflammation score composed of the indicated genes of GALT FRC from PP of donors with CD and CRC. Statistical significance between the samples was determined using a Wilcoxon rank sum test. **P < 0.01; ****P < 0.0001; differences with a P value <0.05 were considered statistically significant. (E) Original UMAP representation of the cross-tissue chronic disease stromal cell atlas by Korsunsky et al. (2022) (left plot) and overlay of the GALT FRC signature (top 10 DEG) on the dataset (right panel). Red circles indicate the location of the proinflammatory CXCL10⁺CCL19⁺ FRC cluster (cluster 11) identified by Korsunsky et al. (2022). (F) Spearman correlation plot showing the overlap between the GALT FRC cluster identified in this study and the indicated FRC clusters described by Korsunsky et al. (2022). Cluster 11 represents the disease activity-associated CXCL10⁺CCL19⁺ FB cluster (Korsunsky et al., 2022). UC, ulcerative colitis; SS, Sjögren’s syndrome; RA, rheumatoid arthritis.