Elucidating the fibrotic niche and cellular dynamics in crohn’s disease-associated fibrostenosis

Dataset overview

Participants 2

Samples 2

Reuse readiness 7.4/10 evidence-backed score

Elucidating a Myofibroblast-dominated Fibrotic Niche in Crohn's Disease-associated Fibrostenosis Through High-resolution Spatial Transcriptomics.

Zhang D, Zou X, He M, Sun S, Yu A, Shi J, Ouyang T, Lin X, et al. · Cellular and molecular gastroenterology and hepatology · 2025

Abstract

<h4>Background & aims</h4>Fibrostenosis is a major complication of Crohn's disease (CD) characterized by intestinal remodeling and excessive extracellular matrix (ECM) deposition. A prominent feature is bowel wall muscularization, involving expansion of submucosal myoid cells and muscularis propria smooth muscle cell (SMC) hyperplasia. However, the cellular identity and molecular mechanisms underlying submucosal myoid cell hyperplasia remain poorly characterized.<h4>Methods</h4>Preoperative intestinal ultrasound from 117 patients with CD was retrospectively reviewed, and ileal tissues from 25 normal, 35 nonstenotic CD, and 44 stenotic CD cases were analyzed histologically. High-resolution spatial transcriptomics was applied to 1 nonfibrotic and 1 fibrostenotic ileal specimen with marked submucosal myoid cell expansion. Findings were validated using public single-cell RNA sequencing datasets (N = 158), immunofluorescence, primary pericyte cultures, and quantitative polymerase chain reaction.<h4>Results</h4>Submucosal myoid cells were predominantly identified as high ECM-producing myofibroblasts, possibly representing the dominant stromal population expanded in fibrotic submucosa. Spatial and pseudotemporal analyses demonstrated their origin from muscularis mucosae and submucosal vascular SMCs. Additionally, pericytes underwent significant expansion and transcriptional reprogramming toward a myofibroblast-like phenotype. Fibroblast sub-clustering revealed spatial heterogeneity, with FAP<sup>+</sup> fibroblasts enriched specifically in fibrotic regions. Inflammatory monocytes colocalized with stromal cells, exhibiting robust predicted ligand-receptor interactions indicative of immune-stromal crosstalk.<h4>Conclusions</h4>This case-level, high-resolution spatial analysis delineates a spatially organized fibrotic niche within a CD stricture, composed of distinct stromal and immune populations. We define the identity and origins of profibrotic myofibroblasts and characterize pericyte-to-myofibroblast reprogramming, thereby highlighting specific cell subtypes as prime therapeutic targets for antifibrotic strategies.

doi:10.1016/j.jcmgh.2025.101701 ↗ PMID 41344440 ↗ PMC12973726 ↗

Study facts

Organism: Homo sapiens
Platform: 10x Genomics Visium HD
Age group: —
Disease groups: Crohn's disease
Anatomical sites: The strictured and fibrotic ileum sample from Crohn's disease patient., The non-strictured and non-fibrotic ileum sample from Crohn's disease patient.

Data availability

Raw counts
Processed matrix
Spatial coordinates
Histology images
Analysis code

File types CSVJPGJSONMTXPNGTSV

ileum2

Accession	Sample	Tissue	Molecule
`GSM9106293`	CD1	ileum	polyA RNA
`GSM9106294`	CD2	ileum	polyA RNA

Strengths & limitations for reuse

Strengths

Raw counts are advertised
Processed matrices are advertised
Spatial coordinates are advertised
Histology images are advertised
Analysis code is available
Participant counts are documented

Extraction evidence & provenance

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

Assay

Field	Value	Evidence
`assay.number_of_cells_or_spots`	989000 inferred	The nonfibrotic and fibrotic tissues yielded ∼469,000 and ∼520,000 spots, respectively Section `Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD`, offset 11600
`assay.platform`	10x Genomics Visium HD	The Visium HD high-resolution spatial transcriptomics platform Section `Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD`, offset 10500
`assay.platform_version`	Visium HD FFPE	Visium HD Spatial Gene Expression Reagent Kits Section `Visium HD library preparation and sequencing`, offset 67500
`assay.reference_genome`	GRCh38 from source	GRCh38 Section `GEO family SOFT`, offset —
`assay.resolution`	cellular	The Visium HD high-resolution spatial transcriptomics platform provides single-cell scale spatial resolution Section `Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD`, offset 11100
`assay.segmentation_method`	8 × 8 μm spot binning	We binned spots into 8 × 8 μm to approximate individual cell areas. Section `Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD`, offset 11400
`assay.sequencing_based`	True from source	GEO assay type/library strategy: OTHER Section `GEO family SOFT`, offset —

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.crohns_disease_participants`	2	1 nonfibrotic and 2 fibrotic ileal specimen from 2 patients with CD Section `Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD`, offset 10500
`cohort.study_design`	cross_sectional inferred	Ileal surgical tissues from CD patients, including strictured and non-strictured regions, were used for spatial transcriptomic analysis. Section `series_overall_design`, offset 2200
`cohort.total_participants`	2	high-resolution spatial transcriptomic profiling on 1 nonfibrotic and 2 fibrotic ileal specimen from 2 patients with CD Section `Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD`, offset 10500

cohort.crohns_disease_participants

2

1 nonfibrotic and 2 fibrotic ileal specimen from 2 patients with CD

Section Identification of a Distinct Submucosal Fibrotic Niche in Fibrostenotic CD, offset 10500

cohort.study_design

cross_sectional inferred

Ileal surgical tissues from CD patients, including strictured and non-strictured regions, were used for spatial transcriptomic analysis.

Section series_overall_design, offset 2200

cohort.total_participants

2

high-resolution spatial transcriptomic profiling on 1 nonfibrotic and 2 fibrotic ileal specimen from 2 patients with CD