ArticleCellular and molecular gastroenterology and hepatology2018
The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- The potential for malignancy from atopic disorders and allergic inflammation: A systematic review and meta-analysis.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2020Pooled it
- Microphysiological models of human gastrointestinal diseases.Nature biomedical engineering · 2026Review
- Esophagus extracellular matrix with microenvironmental complexity for esophageal organoids.Bioactive materials · 2026Article
- Article
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- Deep Invaginations of Nuclear Envelope Coordinate Spatial Organization of Chromatin in Epithelium.bioRxiv : the preprint server for biology · 2026Article
- Oesophageal Epithelial Cell-Intrinsic MHCII Regulates Food Antigen-Dependent Eosinophilic Esophagitis in an IFNγ-Dependent Manner.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Eosinophilic oesophagitis: pathophysiology, diagnosis, and treatment.BMJ medicine · 2026Review
- Overlapping type 2, barrier, and remodeling endotypes shape clinical expression in eosinophilic esophagitis.Frontiers in immunology · 2026Review
- Alarmin Levels and Gastroesophageal Reflux Disease in Children: Significant Elevation of Thymic Stromal Lymphopoietin.Pediatric reports · 2025Article
- Article
- Physiologic and molecular effects of alcohol in the esophagus: a narrative review.Annals of esophagus · 2025Article
- FOXM1 Modulation Alleviates Epithelial Remodeling and Inflammation in Eosinophilic Esophagitis.bioRxiv : the preprint server for biology · 2025Article
- The application of organoids in investigating immune evasion in the microenvironment of gastric cancer and screening novel drug candidates.Molecular cancer · 2025Review
- Epithelial architecture and signaling activity in the adult human esophagus.Frontiers in cell and developmental biology · 2025Review
- Biomedical applications of organoids derived from the digestive system.Frontiers in cell and developmental biology · 2025Review
- Modeling methods of different tumor organoids and their application in tumor drug resistance research.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Lysyl Oxidase Mediates Proliferation and Differentiation in the Esophageal Epithelium.Biomolecules · 2024Article
- Amniotic fluid modifies esophageal epithelium differentiation and inflammatory responses.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids.Biomolecules · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsAberrations in the esophageal proliferation-differentiation gradient are histologic hallmarks in eosinophilic esophagitis (EoE) and gastroesophageal reflux disease. A reliable protocol to grow 3-dimensional (3D) esophageal organoids is needed to study esophageal epithelial homeostasis under physiological and pathologic conditions.
methodsWe modified keratinocyte-serum free medium to grow 3D organoids from endoscopic esophageal biopsies, immortalized human esophageal epithelial cells, and murine esophagi. Morphologic and functional characterization of 3D organoids was performed following genetic and pharmacologic modifications or exposure to EoE-relevant cytokines. The Notch pathway was evaluated by transfection assays and by gene expression analyses in vitro and in biopsies.
resultsBoth murine and human esophageal 3D organoids displayed an explicit proliferation-differentiation gradient. Notch inhibition accumulated undifferentiated basal keratinocytes with deregulated squamous cell differentiation in organoids. EoE patient-derived 3D organoids displayed normal epithelial structure ex vivo in the absence of the EoE inflammatory milieu. Stimulation of esophageal 3D organoids with EoE-relevant cytokines resulted in a phenocopy of Notch inhibition in organoid 3D structures with recapitulation of reactive epithelial changes in EoE biopsies, where Notch3 expression was significantly decreased in EoE compared with control subjects.
conclusionsEsophageal 3D organoids serve as a novel platform to investigate regulatory mechanisms in squamous epithelial homeostasis in the context of EoE and other diseases. Notch-mediated squamous cell differentiation is suppressed by cytokines known to be involved in EoE, suggesting that this may contribute to epithelial phenotypes associated with disease. Genetic and pharmacologic manipulations establish proof of concept for the utility of organoids for future studies and personalized medicine in EoE and other esophageal diseases.
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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.