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Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis - Visium Spatial Transcriptomics

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Dataset overview

Participants None
Samples 36
Reuse readiness 5.4/10 evidence-backed score

Spatial fibroblast niches define Crohn's fistulae.

McGregor C, Qin X, Jagielowicz M, Gupta T, Yin Z, Lentsch V, Fawkner-Corbett D, Wien Lai V, et al. · Nature · 2025

Abstract

Crohn's disease often presents with fistulae, abnormal tunnels that connect the intestine to the skin or other organs. Despite their profound effect on morbidity, the molecular basis of fistula formation remains unclear, largely owing to the challenge of capturing intact fistula tracts and their inherent heterogeneity<sup>1-3</sup>. Here we construct a subcellular-resolution spatial atlas of 68 intestinal fistulae spanning diverse anatomical locations. We describe fistula-associated epithelial, immune and stromal cell states, revealing abnormal zonation of growth factors and morphogens linked to establishment of tunnelling anatomy. We identify fistula-associated stromal (FAS) fibroblasts, which are assembled in concentric layers: a proliferative, lumen-adjacent zone beneath neutrophil and macrophage-rich granulation tissue, an active lesion core of FAS cells and a quiescent, pro-fibrotic outer zone. We examine the architecture of the extracellular matrix in the fistula tract and demonstrate that FAS populations associate with distinct collagen structures, exhibiting properties ranging from proliferation, migration and extracellular matrix remodelling to dense collagen deposition and fibrosis. We define niches supporting epithelialization of fistula tunnels and a FAS-like population that is detected at the base of ulcers in non-penetrating Crohn's disease. Our study demonstrates that common molecular pathways and cellular niches underpin fistulae across intestinal locations, revealing the cellular protagonists of fistula establishment and persistence. This resource will inform the development of model systems and interventions to mitigate aberrant fibroblast activity while preserving their regenerative properties in Crohn's disease.

doi:10.1038/s41586-025-09744-y ↗ PMID 41224999 ↗ PMC12804086 ↗

Study facts

Organism
Homo sapiens
Platform
10x Genomics Visium Spatial Transcriptomics
Age group
adult
Disease groups
—
Anatomical sites
intestine

Data availability

  • Raw counts
  • Spatial coordinates
  • Histology images

File types ZIP

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Spatial coordinates are advertised
  • Histology images are advertised

Limitations

  • Not documented: processed matrices are advertised
  • 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.number_of_cells_or_spots 93075
we sequenced 93,075 tissue-covered spots using the unbiased Visium ST platform

Section Spatial mapping of fistulating CD, offset 4900
assay.platform 10x Genomics Visium Spatial Transcriptomics
This study employed Visium FFPE spatial transcriptomics

Section series_overall_design, offset 5400
assay.platform_version Visium FFPE Spatial Gene Expression
10X Genomics Visium Spatial Gene Expression (CG000408 and CG000409 rev. D) was followed

Section Methods — Visium FFPE protocol, offset 1020500
assay.reference_genome hg38 from source
hg38

Section GEO family SOFT, offset —
assay.resolution spot
we sequenced 93,075 tissue-covered spots using the unbiased Visium ST platform

Section Spatial mapping of fistulating CD, offset 4900
assay.sequencing_based True from source
GEO assay type/library strategy: OTHER

Section GEO family SOFT, offset —
assay.whole_transcriptome True
Visium Human Transcriptome Probe Set v.v1.0_GRCh38-2020-A

Section Methods — Computational analysis, offset 1034200

Cohort

FieldValueEvidence
cohort.age_group adult
Written informed consent was obtained from adult patients undergoing elective or emergency IBD surgery

Section Methods — Human tissue samples, offset 56200
cohort.study_design cross_sectional inferred
A total of 36 slides were analyzed, comprising tissue sections from patients diagnosed with Crohn's disease and non-diseased controls.

Section series_overall_design, offset 1200

Data_Assets

FieldValueEvidence
data_assets.file_manifest True from source
Supplementary files enumerated in family SOFT ()

Section GEO family SOFT, offset —
data_assets.histology_images True
Zip file contains Spaceranger output raw counts matrices, H&E images, spatial coordinates and image scaling factors

Section sample data_processing, offset 2600
data_assets.open_access True
Public on Sep 30 2025

Section series_status, offset 170
data_assets.raw_counts True
Supplementary files format and content: Zip file contains Spaceranger output raw counts matrices, H&E images, spatial coordinates and image scaling factors

Section sample data_processing, offset 2600
data_assets.spatial_coordinates True
Zip file contains Spaceranger output raw counts matrices, H&E images, spatial coordinates and image scaling factors

Section sample data_processing, offset 2600

Specimens

FieldValueEvidence
specimens.anatomical_sites ['intestine'] from source
GEO sample source names: intestine

Section GEO family SOFT, offset —
specimens.number_of_samples 36 computed
36 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.preservation_method formalin-fixed paraffin-embedded (FFPE)
Archived diagnostic formalin-fixed paraffin-embedded (FFPE) blocks for ST and validation were obtained

Section Methods — Human tissue samples, offset 56700
specimens.specimen_type resection
Full-thickness resection tissue samples, surplus to clinical needs, were obtained by the operating surgeon

Section Methods — Sample collection, handling and processing, offset 1009800