ArticleMed (New York, N.Y.)2024
Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease.
Article in Med (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Biomarkers in the pathogenesis and diagnosis of Crohn's perianal fistulas: a systematic review.Techniques in coloproctology · 2026Pooled it
- Single-cell analysis of chromatin accessibility in the human intestine identifies regulatory programs and clarifies genetic associations in Crohn's disease.Nature genetics · 2026Article
- Article
- Epigenetic modulation of stromal cell states underpins pathological tissue niches in Crohn's disease.Nature immunology · 2026Article
- IBD Care Across Diverse Patient Populations: Changing the Narrative.Digestive diseases and sciences · 2026Review
- Crohn's Disease: From Immune Dysregulation to Intestinal Damage.Inflammation · 2026Review
- IL11+ fibroblasts are implicated in nonresponse to anti-TNF-α via fibrosis in inflammatory bowel disease.JCI insight · 2026Article
- Deciphering immune and cellular reprogramming during the progression from inflammatory bowel disease to colorectal cancer using multi-omics single-cell and spatial transcriptomics.Journal of translational medicine · 2026Article
- Spatial multi-omics-guided drug development in inflammatory bowel disease: from mucosal immune niches to precision therapy.Frontiers in immunology · 2026Review
- Mechanical stress-induced STAT3/YAP signaling in fibroblasts programs immunosuppressive lymph node remodeling in lung squamous carcinoma.International journal of biological sciences · 2026Article
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Multimodal biomarkers and prediction models for stricturing and penetrating progression in Crohn's disease.Frontiers in medicine · 2026Review
- Spatial fibroblast niches define Crohn's fistulae.Nature · 2026Article
- Phenome-wide association study of monogenic inflammatory bowel disease genes in diverse biobanks identifies population-specific and shared Goldilocks alleles: implications for Precision Medicine.Journal of Crohn's & colitis · 2025Article
- Single-cell and spatial transcriptomics of stricturing Crohn's disease highlights a fibrosis-associated network.Nature genetics · 2025Article
- Single-Cell and Spatial Multi-omics Reveal Interferon Signaling in the Pathogenesis of Perianal Fistulizing Crohn's Disease.bioRxiv : the preprint server for biology · 2024Article
- Single-cell transcriptomics of rectal organoids from individuals with perianal fistulizing Crohn's disease reveals patient-specific signatures.Scientific reports · 2024Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCrohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry.
methodsWe profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions. Unstimulated monocytes were chronically cultured in diverse cohorts. A subset was analyzed by single-nucleus RNA + ATAC sequencing.
findingsFistulous tract cells from complete proctectomies demonstrated enrichment of myeloid cells compared to paired rectal tissues. Ligand-receptor analysis highlights myeloid-stromal cross-talk and cellular senescence, with cellular co-localization validated by immunofluorescence. Chitinase-3 like-protein-1 (CHI3L1) is a top upregulated gene in stromal cells from fistulae expressing both destructive and fibrotic gene signatures. Monocyte cultures from patients of African ancestry and controls demonstrated differences in CHI3L1 and oncostatin M (OSM) expression upon differentiation compared to individuals of European ancestry. Activating protein-1 footprints are present in ATAC-seq peaks in stress response genes, including CHI3L1 and OSM; genome-wide chromatin accessibility including JUN footprints was observed, consistent with reported mechanisms of inflammatory memory. Regulon analyses confirm known cell-specific transcription factor regulation and implicate novel ones in fibroblast subsets. All pseudo-bulked clusters demonstrate enrichment of genetic loci, establishing multicellular contributions. In the most significant African American Crohn's genetic locus, upstream of prostaglandin E receptor 4, lymphoid-predominant ATAC-seq peaks were observed, with predicted RORC footprints.
conclusionsPopulation differences in myeloid-stromal cross-talk implicate fibrotic and destructive fibroblasts, senescence, epigenetic memory, and cell-specific enhancers in perianal fistula pathogenesis. The transcriptomic and epigenetic data provided here may guide optimization of promising mesenchymal stem cell therapies for perianal fistula.
fundingThis work was supported by grants U01DK062422, U24DK062429, and R01DK123758.
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