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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 6.7/10 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 FFPE Spatial Gene Expression
Age group
adult
Disease groups
—
Anatomical sites
intestine

Data availability

  • Raw counts
  • Processed matrix
  • Spatial coordinates
  • Histology images

File types ZIP

Strengths & limitations for reuse

Strengths

  • Raw counts are advertised
  • Processed matrices are advertised
  • Spatial coordinates are advertised
  • Histology images are advertised
  • Participant-to-sample mapping 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.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 2300
assay.platform 10x Genomics Visium FFPE Spatial Gene Expression
For the ST experiment, 5-μm sections were placed onto Visium FFPE spatial GEX slides

Section Methods > Visium FFPE protocol, offset —
assay.platform_version Visium FFPE
Visium FFPE protocol

Section Methods > Visium FFPE protocol, offset —
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 — Raw sequencing data processing, offset 100700

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 6790
cohort.disease_activity_metadata_available True
Supplementary Table 1 ... detailing key demographic and clinical variables such as age, sex, diagnosis, disease subtype, anatomical site, inflammation status and treatment history

Section Supplementary information, offset —
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
cohort.treatment_exposure_documented True
Supplementary Table 1 ... detailing key demographic and clinical variables such as age, sex, diagnosis, disease subtype, anatomical site, inflammation status and treatment history

Section Supplementary information, offset 12500

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.participant_metadata True
Supplementary Table 1 ... detailing key demographic and clinical variables such as age, sex, diagnosis, disease subtype, anatomical site, inflammation status and treatment history

Section Supplementary information, offset —
data_assets.processed_matrix True
Zip file contains Spaceranger output raw counts matrices

Section data_processing, offset —
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.sample_metadata True
sample_values_with_sample_counts

Section sample_values_with_sample_counts, offset —
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.inflamed_status_available True
Supplementary Table 1 ... detailing ... inflammation status and treatment history

Section Supplementary information, offset 12500
specimens.number_of_samples 36 computed
36 GSM records parsed from GEO family SOFT

Section GEO family SOFT, offset —
specimens.participant_to_sample_mapping_available True
Supplementary Table 1 Table summarizing clinical characteristics of all patient samples included in the study

Section Supplementary information, offset 12500
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 7600