ArticleCellular and molecular gastroenterology and hepatology2026
Elucidating a Myofibroblast-dominated Fibrotic Niche in Crohn's Disease-associated Fibrostenosis Through High-resolution Spatial Transcriptomics.
Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Myofibroblast-Driven Crohn's Disease Fiber Stricture Fibrotic Microenvironment: High-Resolution Spatial Transcriptomic Analysis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Spatial multi-omics-guided drug development in inflammatory bowel disease: from mucosal immune niches to precision therapy.Frontiers in immunology · 2026Review
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Authors and funding
16 authors.
Funding
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Abstract
BACKGROUND &
aimsFibrostenosis 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.
methodsPreoperative 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.
resultsSubmucosal 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
conclusionsThis 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.
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