ArticleGut2019
DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development.
Article in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 190 citations in OpenAlex.
- Regional organization of nutrient absorption across the small intestine.Nature reviews. Gastroenterology & hepatology · 2026Review
- Microplastics and Nanoplastics in Food: Dietary Toxicology Beyond Particle Counts.Comprehensive reviews in food science and food safety · 2026Review
- Current smoking and COPD are associated with differentiation-dependent secretory and inflammatory programs in airway basal cells.Respiratory research · 2026Article
- TET Enzymes as Epigenetic Integrators in Intestinal Immunity, Inflammation, and Disease.Journal of personalized medicine · 2026Review
- Inhibition of DNA demethylation attenuates experimental necrotizing enterocolitis via suppression of TLR4-mediated inflammation.Research square · 2026Article
- Disease-derived liver organoids as a preclinical screening platform identify Sargassum japonica as an anti-fibrotic candidate.Scientific reports · 2026Article
- Equine endometrial organoids preserve tissue structure and cycle-stage transcriptional identity†.Biology of reproduction · 2026Article
- Derivation, expansion and cryopreservation of primary fetal organoids from second and third trimester human amniotic fluid cells.Nature protocols · 2026Review
- Tendon Organoids Enable Functional Tendon Rejuvenation Through ALKBH5-Dependent RNA Demethylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Intestinal Stem Cells From Patients With Inflammatory Bowel Disease Retain an Epigenetic Memory of Inflammation.Cellular and molecular gastroenterology and hepatology · 2026Article
- Pathogenesis of adherent-invasiveGut microbes · 2025Article
- Defining the Antitumor Mechanism of Action of a Clinical-stage Compound as a Selective Degrader of the Nuclear Pore Complex.Cancer discovery · 2025Article
- Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition.bioRxiv : the preprint server for biology · 2025Article
- Human intestinal enteroids: Nonclinical applications for predicting oral drug disposition, toxicity, and efficacy.Pharmacology & therapeutics · 2025Review
- Automated tissue dissociation for the establishment of human intestinal organoids.Scientific reports · 2025Article
- Bat organoids reveal antiviral responses at epithelial surfaces.Nature immunology · 2025Article
- Epigenetic modulation of the NLRP6 inflammasome sensor as a therapeutic modality to reduce necroptosis-driven gastrointestinal mucosal dysfunction in HIV/SIV infection.Cell communication and signaling : CCS · 2025Article
- Robust and reproducible human intestinal organoid-derived monolayer model for analyzing drug absorption.Scientific reports · 2025Article
- Review
- TheBiomolecules · 2025Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveHuman intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited.
designWe performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology.
resultsWe discovered stable epigenetic signatures which define regional differences in gut epithelial function, including induction of segment-specific genes during cellular differentiation. Established DNA methylation profiles were independent of cellular environment since organoids retained their regional DNA methylation over prolonged culture periods. In contrast to paediatric and adult organoids, fetal gut-derived organoids showed distinct dynamic changes of DNA methylation and gene expression in culture, indicative of an in vitro maturation. By applying CRISPR/Cas9 genome editing to fetal organoids, we demonstrate that this process is partly regulated by TET1, an enzyme involved in the DNA demethylation process. Lastly, generating IEOs from a child diagnosed with gastric heterotopia revealed persistent and distinct disease-associated DNA methylation differences, highlighting the use of organoids as disease-specific research models.
conclusionsOur study demonstrates striking similarities of epigenetic signatures in mucosa-derived IEOs with matching primary epithelium. Moreover, these results suggest that intestinal stem cell-intrinsic DNA methylation patterns establish and maintain regional gut specification and are involved in early epithelial development and disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.