ArticleJCI insight2023
EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking.Life science alliance · 2026Article
- Regional organization of nutrient absorption across the small intestine.Nature reviews. Gastroenterology & hepatology · 2026Review
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells.Nature biotechnology · 2026Article
- Mapping mesenchymal diversity in the human small intestine and organoids.Nature cell biology · 2026Article
- Dynamic Reprogramming of PDGFRA-Expressing Stromal Cells Facilitates WNT-Driven Transformation by Promoting a Fetal-Like State in the Intestinal Epithelium.Cancer research · 2026Article
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Dictionary of human intestinal organoid responses to secreted niche factors at single cell resolution.Nature communications · 2026Article
- Organoid models: applications and research advances in gastric cancer.Frontiers in oncology · 2026Review
- Polarized Distribution of Lipid Droplets with Long Acyl Chains and Unsaturation are Hallmarks of Human Intestinal Enteroid Differentiation.Analytical chemistry · 2025Article
- EGFR activation in cholangiocytes promotes extrahepatic bile duct regeneration after injury.Hepatology communications · 2025Article
- Fibroblasts enhance the growth and survival of adult feline small intestinal organoids.mSphere · 2025Article
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- Recent evolution of the developing human intestine affects metabolic and barrier functions.Science (New York, N.Y.) · 2025Article
- Structure and organization of full-length epidermal growth factor receptor in extracellular vesicles by cryo-electron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature.Cell stem cell · 2025Article
- Functional maturation of preterm intestinal epithelium through CFTR activation.Communications biology · 2025Article
- Harnessing 3D models to uncover the mechanisms driving infectious and inflammatory disease in the intestine.BMC biology · 2024Review
- BEST4American journal of physiology. Cell physiology · 2024Review
- RTK signalling promotes epithelial columnar cell shape and apical junction maintenance in human lung progenitor cells.Development (Cambridge, England) · 2023Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt. Enteroids generated from the developing human intestine grown in standard culture conditions, which contain EGF, are dominated by stem and progenitor cells and feature little differentiation and no spatial organization. Our results demonstrate that EREG can replace EGF in vitro, and EREG leads to spatially resolved enteroids that feature budded and proliferative crypt domains and a differentiated villus-like central lumen. Multiomic (transcriptome plus epigenome) profiling of native crypts, EGF-grown enteroids, and EREG-grown enteroids showed that EGF enteroids have an altered chromatin landscape that is dependent on EGF concentration, downregulate the master intestinal transcription factor CDX2, and ectopically express stomach genes, a phenomenon that is reversible. This is in contrast to EREG-grown enteroids, which remain intestine like in culture. Thus, EREG creates a homeostatic intestinal niche in vitro, enabling interrogation of stem cell function, cellular differentiation, and disease modeling.
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Registered trials
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.