Extended Data Fig. 1: Spatial atlas of Crohn’s fistulae.

Related to Fig. 1. A. Haematoxylin and eosin (H&E) tissue section from healthy ileum displaying characteristic full-thickness bowel layers, including mucosa (MUC), muscularis mucosae (MM), submucosa (SM) and muscularis propria (MP). n = 92 total samples imaged. B. Haematoxylin and eosin (H&E) tissue section from colonic CD fistula showing loss of the lining columnar epithelium (black arrow) toward the fistula tract (arrowheads). The fistula tract is lined with granulation tissue exhibiting neovascularisation. n = 92 total samples imaged. C. Haematoxylin and eosin (H&E) tissue section from ileocolonic CD fistula (arrowheads) lacking lining epithelium, with mesenteric adipose tissue (MAT), an inflammatory infiltrate and lymphoid follicle (LF) formation. Adjacent mural abscess formation (+) and disruption of the muscularis propria (asterisk) are evident. n = 92 total samples imaged. D. Haematoxylin and eosin (H&E) tissue section from colonic CD fistula demonstrating epithelial loss along the fistula tract (arrowheads) with underlying submucosal fibrosis. Granulation tissue, neovascularisation and dense inflammatory infiltration line the tract. n = 92 total samples imaged. E. Haematoxylin and eosin (H&E) tissue section from epithelialised ileocolonic CD fistula (arrowheads) originating from the ileocecal valve. The fistula tracts branch deep into the muscularis propria, disrupting muscle fibres (asterisk), but do not penetrate all intestinal layers or extend into MAT. While no acute inflammation is present, fibrotic scarring is evident through hypertrophy of the muscularis propria and submucosal fibrosis. n = 92 total samples imaged. F. UMAP visualisation of integrated data across scRNA-Seq cohort summarised in Fig. 1b. Each point represents a cell, points are coloured by broad cell types. n = 22 donors, n = 82 samples, n = 129,204 cells. G. UMAP visualisation of integrated data across Visium ST cohort, summarised in Fig. 1b. Each point represents a tissue covered spot, points are coloured by broad tissue regions. n = 34 samples, n = 93,075 spots. H. UMAP visualisation of integrated data across Xenium ST cohort, summarised in Fig. 1b. Each point represents a cell, points are coloured by broad cell types. n = 53 samples, n = 7,268,690 cells. I. A representative tissue section from an epithelialised, perianal fistula stained with H&E (n = 92 samples), with dashed lines indicating a region selected for profiling with Visium ST in black, and Xenium ST in red. J. Visium ST spot cluster overlay of tissue section shown in I, with reference UMAP embedding and region annotation visualised in G. (n = 34 samples). K. Xenium ST cell type cluster overlay of tissue section shown in I, with reference UMAP embedding and cell type annotation visualised in H. Dashed blue lines indicate a smaller ROI visualised in I-N. (n = 53 samples). L. Zoomed in view visualising ROI indicated by dashed blue lines in panel K. Each point represents a centroid of a cell, with cells coloured by cell type as indicated in panel H. M. Zoomed in view visualising ROI indicated by dashed blue lines in panel K, visualising expression of an epithelial cell marker gene EPCAM. N. Zoomed in view visualising ROI indicated by dashed blue lines in panel K, visualising expression of a fibroblast cell marker gene ADAMDEC1.