ArticleCellular and molecular gastroenterology and hepatology2022
Single-Cell Analysis Reveals Unexpected Cellular Changes and Transposon Expression Signatures in the Colonic Epithelium of Treatment-Naïve Adult Crohn's Disease Patients.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Notch receptors involved in the choice between intestinal secretory and enterocytes and differentiation of Bestrophin4 cells.Developmental biology · 2026Article
- Single-Cell and Spatial Transcriptomics Across Populations With Perianal Fistulizing Crohn's Disease Shows Proinflammatory CD4Cellular and molecular gastroenterology and hepatology · 2026Article
- Single-cell RNA sequencing of terminal ileal biopsies identifies signatures of Crohn's disease pathogenesis.Nature genetics · 2026Article
- Downregulation of MLL1 Promotes Intestinal Epithelial Barrier Repair Through Gata4/Bmp4 Activation to Ameliorate Crohn's Disease-Like Colitis in Mice.Cell proliferation · 2026Article
- Colonic epithelial regeneration shapes susceptibility tobioRxiv : the preprint server for biology · 2026Article
- Integrated single-cell transcriptomic atlas of human gastric and colorectal tissues across diverse phenotypes.Scientific data · 2026Article
- Single-Cell Comparison of Small Intestinal Neuroendocrine Tumors and Enterochromaffin Cells from Two Patients.Cancers · 2026Article
- Intestinal epithelial TLR5 signaling promotes barrier-supportive macrophages.Science immunology · 2026Article
- Transcriptome and microbiota analysis reveal differences in the cecum of weaning pigs in response to different dietary crude protein levels.Animal bioscience · 2026Article
- Single-cell transcriptome analyses reveal disturbed decidual microenvironment in women of advanced maternal age.Clinical and translational medicine · 2025Article
- Akkermansia muciniphila-Derived N-Acetylspermidine Modulates the Localization of Intestinal α1,2-Fucosylated Proteins to Maintain Gut Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Distinct Retrotransposon Transcriptome in Pediatric Crohn's Disease.Inflammatory bowel diseases · 2025Article
- PIWIL2 downregulation in colon cancer promotes transposon activity and pro-tumorigenic phenotypes.Biology open · 2025Article
- Bacteroides Fragilis-Derived Outer Membrane Vesicles Deliver MiR-5119 and Alleviate Colitis by Targeting PD-L1 to Inhibit GSDMD-Mediated Neutrophil Extracellular Trap Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction.PLoS computational biology · 2025Article
- Differential effects of tofacitinib on macrophage activation contribute to lack of response in ulcerative colitis patients.Journal of Crohn's & colitis · 2025Article
- ITLN1 exacerbates Crohn's colitis by driving ZBP1-dependent PANoptosis in intestinal epithelial cells through antagonizing TRIM8-mediated CAPN2 ubiquitination.International journal of biological sciences · 2025Article
- Differential analysis of sorting nexin 10 and sterol regulatory element-binding protein 2 expression in inflammatory bowel disease.Immunologic research · 2024Article
- Decoding the mosaic of inflammatory bowel disease: Illuminating insights with single-cell RNA technology.Computational and structural biotechnology journal · 2024Review
- Vagal stimulation ameliorates murine colitis by regulating SUMOylation.Science translational medicine · 2024Article
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type-specific therapeutic targets. We performed, at single-cell resolution, a direct comparison of the colonic epithelial cellular and molecular landscape between treatment-naïve adult CD and non-inflammatory bowel disease control patients.
methodsColonic epithelial-enriched, single-cell sequencing from treatment-naïve adult CD and non-inflammatory bowel disease patients was investigated to identify disease-induced differences in IEC types.
resultsOur analysis showed that in CD patients there is a significant skew in the colonic epithelial cellular distribution away from canonical LGR5+ stem cells, located at the crypt bottom, and toward one specific subtype of mature colonocytes, located at the crypt top. Further analysis showed unique changes to gene expression programs in every major cell type, including a previously undescribed suppression in CD of most enteroendocrine driver genes as well as L-cell markers including GCG. We also dissect an incompletely understood SPIB+ cell cluster, revealing at least 4 subclusters that likely represent different stages of a maturational trajectory. One of these SPIB+ subclusters expresses crypt-top colonocyte markers and is up-regulated significantly in CD, whereas another subcluster strongly expresses and stains positive for lysozyme (albeit no other canonical Paneth cell marker), which surprisingly is greatly reduced in expression in CD. In addition, we also discovered transposable element markers of colonic epithelial cell types as well as transposable element families that are altered significantly in CD in a cell type-specific manner. Finally, through integration with data from genome-wide association studies, we show that genes implicated in CD risk show heretofore unknown cell type-specific patterns of aberrant expression in CD, providing unprecedented insight into the potential biological functions of these genes.
conclusionsSingle-cell analysis shows a number of unexpected cellular and molecular features, including transposable element expression signatures, in the colonic epithelium of treatment-naïve adult CD.
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