Fig. 1: Fistula-associated fibroblast states lining fistula tracts.

a, Schematic overview of the experimental design for spatial and single-cell analyses. FFPE, formalin-fixed paraffin-embedded sections; NI, non-involved tissue; t-SNE, t-distributed stochastic neighbour embedding. Created in BioRender. Group, S. (2025) https://BioRender.com/2lka2xp. b, Overview of the scRNA-seq and ST cohorts. Each point represents an individual sample. Fist, fistulating; Inf, inflammatory; Inv, involved; N.Inv, non-involved; Stric, stricturing. c, Left, a representative non-epithelialized CD fistulating tissue section profiled with Xenium ST (n = 53 total samples). A paired haematoxylin and eosin (H&E) image is shown in Supplementary Data. Right, closer views of the indicated lesion edge, showing WNT5A and PRRX1 expression. Fistula tract is indicated by white arrows. d, Left, a representative partially epithelialized CD fistulating tissue section profiled with Xenium ST (n = 53 total samples). A paired H&E image is shown in Supplementary Data. Right, closer views of the indicated lesion edge, showing PRRX1, IL11, MMP1 and MMP3 expression. Fistula tract is indicated by white arrows. e, Distance-based analysis with respect to fistula edge, with a representative (n = 13 total sections with a clearly histologically identifiable fistula tract) non-epithelialized fistula tract tissue section visualizing the distance of each cell centroid from the edge of the fistula tract. f, Density plot visualizing FAS cell subtype distribution over distance from fistula edge, measured across all fistulae with a clearly histologically identifiable fistula tract (n = 13). Shaded areas around lines show s.e.m. per cell type, representing variation across independent patient sections.