Single-cell spatial transcriptomics of formalin-fixed, paraffin-embedded biopsies reveals colitis-associated cell networks [Xenium]

Here, we developed, benchmarked, and applied a robust framework for applying iSCST to clinical FFPE mucosal biopsies from patients with UC, immune checkpoint inhibitor-induced (ICI) colitis and healthy controls. iSCST using custom Xenium gene panels enabled precise detection of diverse cell subsets and disease-specific genes.

We mapped transcriptionally distinct fibroblast subsets within mucosal niches, including inflammation-associated fibroblasts (IAFs), and identified colitis-specific neighborhoods formed by IAFs, monocytes, and neutrophils. Transcriptional signatures uncovered through iSCST were associated with vedolizumab (VDZ) response, with non-responders exhibiting either an IAF-monocyte signature or adaptive gut-associated lymphoid tissue (GALT) signature, while responders showed enrichment of epithelial gene expression.