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

ABSTRACT: Imaging-based single-cell spatial transcriptomics (iSCST) on formalin-fixed, paraffin-embedded (FFPE) tissue enables comprehensive analysis of archived specimens while preserving spatial context, critical to an understanding of ulcerative colitis (UC) pathology. 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. These signatures were validated in both internal and publicly-available external datasets. This iSCST framework provides a powerful approach for analyzing FFPE tissues, offering insights into colitis-associated cellular networks and identifying biomarkers to enhance patient risk stratification in routine clinical workflows.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282123 | GEO | 2026/05/21

REPOSITORIES: GEO

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

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