Table 2_A full-thickness spatial transcriptomics atlas of medically refractory ulcerative colitis identifies niche signatures associated with biologic non-response.xlsx

Background<p>Ulcerative colitis (UC) is a chronic mucosal immune disorder in which 30-50% of patients fail biologic therapy, yet the full-thickness immune architecture of medically refractory disease and reliable tissue-level markers of treatment response remain undefined.</p>Methods<p>Using 10x Visium HD spatial transcriptomics (16-µm bins; 615,274 bins), we generated a full-thickness spatial atlas of surgically resected colon from patients with medically refractory UC (n=3) and controls (n=3), integrating niche-stratified differential expression, spatial cell–cell communication, SCENIC regulon inference and single-sample GSEA with immunofluorescence and DSS-colitis flow cytometry.</p>Results<p>We resolved 18 spatial immune–stromal niches across five tissue modules.

At the mucosal frontline, epithelial barrier collapse was accompanied by a 20-fold expansion of ulcer-bed stroma (p=0.030) that co-localised with an Acute Neutrophil Niche and was associated with neutrophil recruitment via CXCL12–CXCR4 signalling, forming a spatially integrated ulcerogenic unit. In the submucosa, a humoral immune programme was associated with tertiary lymphoid structures (TLS) and plasma-cell survival-related signalling (MIF–CD74 and LTB–CD40).