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← IBD spatial transcriptomics

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

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Dataset overview

Participants None
Samples 7
Reuse readiness 7.9/10 evidence-backed score

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

Mennillo E, Lotstein ML, Lee G, Hou JH, Johri V, Leet DE, Ekstrand CA, Tsui J, et al. · The Journal of clinical investigation · 2026

Abstract

Imaging-based, single-cell, spatial transcriptomics (iSCST) of FFPE tissue enables comprehensive analysis of archived specimens while preserving spatial context, critical to an understanding of ulcerative colitis (UC) pathology. Here, we deployed a robust framework for applying iSCST to clinical FFPE mucosal biopsies from patients with UC or immune checkpoint inhibitor-induced colitis, as well as patients serving as 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 and spatial neighborhoods uncovered through iSCST were associated with vedolizumab (VDZ) response, with nonresponders exhibiting either an innate IAF-monocyte-neutrophil signature or adaptive gut-associated lymphoid tissue signature, while responders showed enrichment of an epithelial cellular neighborhood. These signatures were validated in an internal and an external dataset, supporting the existence of 2 distinct archetypes of treatment resistance to VDZ in UC. 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.

doi:10.1172/jci202488 ↗ PMID 42262875 ↗ PMC13367960 ↗

Study facts

Organism
Homo sapiens
Platform
Xenium
Age group
—
Disease groups
—
Anatomical sites
Non-IBD controls and patients with ulcerative colitis (UC), Non-IBD controls and patients with either ulcerative colitis (UC) or immune checkpoint inhibitor-induced colitis (ICI)

Data availability

  • Raw counts
  • Processed matrix
  • Spatial coordinates
  • Analysis code

File types TARXLSX

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Processed matrices are advertised
  • Spatial coordinates are advertised
  • Analysis code is available

Limitations

  • Not documented: participant counts are documented
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.platform Xenium
This GEO submission contains the Xenium datasets

Section series_overall_design, offset —
assay.platform_version Xenium In Situ v1 and Xenium Prime v2
xenium in situ assay chemistry: v1 (RNA only)

Section samples.characteristics, offset 500
assay.resolution subcellular
FFPE tissue with subcellular resolution

Section Introduction, offset 500
assay.segmentation_method Nuclear expansion and multimodal cell segmentation
Xenium and CosMx used distinct segmentation methods in Dataset 1 — nuclear expansion (Xenium) and multimodal segmentation (CosMx)

Section Results, offset 4700
assay.sequencing_based False
Imaging-based single-cell spatial transcriptomics (iSCST)

Section series_summary, offset —
assay.whole_transcriptome False
we designed custom panels containing 290 genes (Xenium)

Section Results, offset 2700

Cohort

FieldValueEvidence
cohort.disease_activity_metadata_available True
Biopsy samples were categorized based on the level of inflammation observed endoscopically

Section Study participants and biospecimen collection, offset 700
cohort.study_design longitudinal
retrospective, longitudinal, case-control analyses of archived clinical specimens

Section Introduction, offset 1100
cohort.treatment_exposure_documented True
Response was defined as endoscopic remission ... after completing induction, while nonresponse was defined as persistent moderate-to-severe inflammation

Section Study participants and biospecimen collection, offset 1000
cohort.treatment_response_metadata_available True
Response was defined as endoscopic remission ... while nonresponse was defined as persistent moderate-to-severe inflammation

Section Study participants and biospecimen collection, offset 1000

Data_Assets

FieldValueEvidence
data_assets.analysis_code True
All code necessary for recreating the associated analyses and figures is available on the ... GitHub repository

Section Data availability, offset 1050
data_assets.environment_or_container_info True
Conda environment YAML files

Section Data availability, offset 1200
data_assets.file_manifest True
filelist.txt

Section filelist.txt, offset —
data_assets.molecule_coordinates True
the transcript file (transcripts.csv.gz or transcripts.parquet) for each Xenium run

Section samples.data_processing, offset —
data_assets.open_access True
Public on May 21 2026

Section series_status, offset —
data_assets.participant_metadata True
Baseline demographic and clinical information about the study participants from the 3 datasets are provided in Supplemental Tables 1–3

Section Study participants and biospecimen collection, offset 500
data_assets.processed_matrix True
cell-feature matrix file (cell_feature_matrix.h5)

Section samples.data_processing, offset —
data_assets.raw_counts True
Raw Xenium and MERSCOPE data files are available in the GEO under accession numbers GSE282123 and GSE282124

Section Data availability, offset 500
data_assets.sample_metadata True
characteristics: panel; cell segmentation method; xenium in situ assay chemistry

Section samples, offset —
data_assets.spatial_coordinates True
cell-level gene expression, metadata, and spatial location information

Section Data preprocessing and annotation, offset 700

Specimens

FieldValueEvidence
specimens.anatomical_sites ['Non-IBD controls and patients with ulcerative colitis (UC)', 'Non-IBD controls and patients with either ulcerative colitis (UC) or immune checkpoint inhibitor-induced colitis (ICI)'] from source
GEO sample source names: Non-IBD controls and patients with ulcerative colitis (UC); Non-IBD controls and patients with either ulcerative colitis (UC) or immune checkpoint inhibitor-induced colitis (ICI)

Section GEO family SOFT, offset —
specimens.inflamed_status_available True
Biopsy samples were categorized based on the level of inflammation observed endoscopically

Section Study participants and biospecimen collection, offset 700
specimens.number_of_samples 7 computed
7 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.preservation_method 10% formalin fixation, ethanol processing, and paraffin embedding (FFPE)
Biopsies were placed in 10% formalin for up to 24 h, then ethanol, and then embedded in paraffin

Section Study participants and biospecimen collection, offset 300
specimens.specimen_type biopsy
clinical FFPE mucosal biopsies from patients with UC, immune checkpoint inhibitor-induced colitis and healthy controls

Section series_summary, offset —