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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 v1 and v2
xenium in situ assay chemistry: v1 (RNA only)... v2 (Xenium Prime)

Section sample characteristics, offset —
assay.resolution subcellular
platforms capable of analyzing FFPE specimens with subcellular resolution

Section Results—iSCST approaches on archived FFPE mucosal colon biopsies, offset 3000
assay.segmentation_method Nuclear expansion and multimodal cell segmentation
cell segmentation method: Nuclear expansion... Multimodal (extra staining step in protocol)

Section sample characteristics, offset —
assay.sequencing_based False
Imaging-based single-cell spatial transcriptomics (iSCST)

Section 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
We have consent to publish deidentified patient demographics, including age at the time of sample collection, sex, diagnosis, and medical center.

Section Methods—Study participants and biospecimen collection, offset 43800
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 62000
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 Methods—Study participants and biospecimen collection, offset 44900
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 for long-term storage.

Section Study participants and biospecimen collection, offset 31600
specimens.specimen_type biopsy
clinical FFPE mucosal biopsies from patients with UC, immune checkpoint inhibitor-induced colitis and healthy controls

Section series_summary, offset —