ArticleNature communications2024
Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed.
- Single-cell analysis of chromatin accessibility in the human intestine identifies regulatory programs and clarifies genetic associations in Crohn's disease.Nature genetics · 2026Article
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- A spatial and temporal transcriptomic atlas of mouse intestinal regeneration in the jejunum.Nature communications · 2026Article
- Patient-matched transcriptomics of in vivo and in vitro colonic epithelium substantiate organoids as a translational model for ulcerative colitis.Scientific reports · 2026Article
- Colonic epithelial regeneration shapes susceptibility tobioRxiv : the preprint server for biology · 2026Article
- Microbiome-produced nicotinic acid controls colon regional identity and injury susceptibility.Cell · 2026Article
- Identifying omic biomarkers for chronic inflammatory diseases associated with periodontitis using percolation on multi-disease gene co-expression networks.Communications medicine · 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
- Pathobiont-triggered induction of goblet cell response drives regional susceptibility to inflammatory bowel disease.The Journal of clinical investigation · 2026Article
- Goblet of fire: how Chlamydia ignites region-specific colitis by hijacking goblet cells.The Journal of clinical investigation · 2026Article
- Non-invasive determination of disease activity in Crohn's disease by serum luminex profiling.Scientific reports · 2026Article
- DUOX2-Driven Oxidative Stress Alters the Gut Redox Niche and Promotes Microbial Dysbiosis in Crohn's Disease.Antioxidants (Basel, Switzerland) · 2026Article
- Human DNA levels in feces reflect gut inflammation and associate with presence of gut species in IBD patients across the age spectrum.Microbiome · 2026Article
- Ultrarare Variants in DNA Damage Repair and Mitochondrial Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome and Acute Behavioral Regression in Neurodevelopmental Disorders.Developmental neuroscience · 2026Article
- Dictionary of human intestinal organoid responses to secreted niche factors at single cell resolution.Nature communications · 2026Article
- scSuperAnnotator: a platform for benchmarking comparison and visualizing automated cellular annotation methods for scRNA-seq data.Nucleic acids research · 2026Article
- Generative AI-augmented transcriptomic and microbiome analysis across inflammatory and fibrotic disease states in Crohn's disease.Frontiers in artificial intelligence · 2026Article
- Spatial fibroblast niches define Crohn's fistulae.Nature · 2026Article
- Spatial multi-omics-guided drug development in inflammatory bowel disease: from mucosal immune niches to precision therapy.Frontiers in immunology · 2026Review
- Supplementation with endogenous healthy gut metabolites reverses the disruptions of in vitro and ex vivo epithelial functions induced by fecal content from IBD patients.Gut microbes · 2025Article
Corrections and comments
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Authors and funding
39 authors.
Jia LiCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
Alan J SimmonsEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-3412-5819
Caroline V HawkinsDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Sophie ChironDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Marisol A Ramirez-SolanoCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
Naila TasneemEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0009-0009-6450-9475
Harsimran KaurEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Yanwen XuEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Frank RevettaDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Paige N VegaEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0003-2799-7587
Shunxing BaoDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.
Can CuiDepartment of Computer Science, Vanderbilt University, Nashville, TN, USA.
Regina N TyreeDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Larry W RaberDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Anna N ConnerDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jennifer M PilatDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Justin JacobseDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-1899-0319
Kara M McNamaraDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Margaret M AllamanDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-2803-1365
Gabriella A RaffaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Alain P GobertDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0001-7535-539X
Mohammad AsimDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jeremy A GoettelDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-0749-2357
Yash A ChoksiDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Dawn B BeaulieuDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Robin L DalalDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Sara N HorstDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Baldeep S PablaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Yuankai HuoDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.ORCID 0000-0002-2096-8065
Bennett A LandmanDepartment of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.ORCID 0000-0001-5733-2127
Joseph T RolandEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Elizabeth A ScovilleDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
David A SchwartzDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
M Kay WashingtonProgram in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Yu ShyrCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
Keith T WilsonDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.ORCID 0000-0003-4421-1830
Lori A CoburnDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. lori.coburn@vumc.org.ORCID 0000-0003-3249-9806
Ken S LauCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. ken.s.lau@vanderbilt.edu.ORCID 0000-0001-8438-0319
Qi LiuCenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. qi.liu@vumc.org.ORCID 0000-0001-8892-7078
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2002 to 2026
$29.9MRole of Iron and B-Catenin Activation in Gastric CarcinogenesisP01CA116087 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Maria Blanca Piazuelo · 2009 to 2026
$27.5MVanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STEPHEN W. FESIK · 2019 to 2026
$19.6MRoles for Supermeres in CRC ProgressionP01CA229123 · NCI · VANDERBILT UNIVERSITY · PI Alissa M Weaver · 2020 to 2026
$12.9MTennessee Valley Cooperative Human Tissue NetworkUM1CA183727 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2014 to 2026
$12.6MProject 3 - Differential contribution of thymic APCs to central tolerance during the perinatal to adult transitionP01AI139449 · NIAID · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RICHIE, ELLEN R · 2020 to 2024
$12.0MShaping the Microenvironment by DPEP1 Facilitates Adenoma ProgressionU54CA274367 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Robert J. Coffey · 2022 to 2026
$9.7MTuft cell heterogeneity in function, lineage, and structure in ileal inflammatory diseaseR01DK103831 · NIDDK · VANDERBILT UNIVERSITY · PI LAU, KEN S · 2016 to 2024
$4.4MSpermidine as a New Therapy for Colitis and Chemopreventive for Colitis-associated CarcinogenesisR01DK128200 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 2021 to 2024
$2.7MBCCMA: Targeting Gut-Microbiome in Veterans Deployment Related Gastrointestinal and Liver Diseases: Dysbiosis, PTSD, and Epithelial and Immune Biology in Inflammatory Bowel Disease in VeteransI01CX002473 · VA · VETERANS HEALTH ADMINISTRATION · PI Keith T. Wilson · 2023 to 2026
–BLRD VA I01 BX004366CSRD VA I01 CX002171CSRD VA I01 CX002473Leona M. and Harry B. Helmsley Charitable Trust (Helmsley Charitable Trust) G-1903-03793NCATS NIH HHS UL1 TR000445NCI NIH HHS P01 CA116087NCI NIH HHS P01 CA229123NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA236733NCI NIH HHS U54 CA274367NCI NIH HHS UM1 CA183727NIAID NIH HHS P01 AI139449NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK103831NIDDK NIH HHS R01 DK128200
Abstract
Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.
Indexed as
ColonCrohn DiseaseDual OxidasesEpithelial CellsIleumLipocalin-2AdultFemaleHumansIntestinal MucosaMaleMiddle AgedNitric Oxide Synthase Type IITumor Necrosis Factor-alphaDual OxidasesDUOX2 protein, humanLCN2 protein, humanLipocalin-2Nitric Oxide Synthase Type IINOS2 protein, humanTumor Necrosis Factor-alpha
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