{"doi":"10.3390/biom14091126","title":"Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids","abstract":"Background: Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco’s Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state. Methods: We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids. To optimize the ADF-based medium, we evaluated the requirement of exogenous epidermal growth factor (EGF) and inhibition of transforming growth factor-(TGF)-β receptor-mediated signaling, both key regulators of the proliferation of human esophageal keratinocytes. We have modeled human esophageal epithelial pathology by stimulating esophageal 3D organoids with interleukin (IL)-13, an inflammatory cytokine, or UAB30, a novel pharmacological activator of retinoic acid signaling. Results: The formation of normal human esophageal 3D organoids was limited by excessive EGF and intrinsic TGFβ-receptor-mediated signaling. Optimized HOME0 improved normal human esophageal organoid formation. In the HOME0-grown organoids, IL-13 and UAB30 induced epithelial changes reminiscent of basal cell hyperplasia, a common histopathologic feature in broad esophageal disease conditions including eosinophilic esophagitis. Conclusions: HOME0 allows modeling of the homeostatic differentiation gradient and perturbation of the human esophageal epithelium while permitting a comparison of organoids from mice and other organs grown in ADF-based media.","journal":"Biomolecules","year":2024,"id":456442,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":943379,"name":"Masaki Morimoto","orcid":"0000-0001-5937-4056","position":1,"is_corresponding":false},{"id":1280847,"name":"Wataru Hirose","orcid":"0000-0001-9095-6951","position":2,"is_corresponding":false},{"id":750526,"name":"Yasuto Tomita","orcid":null,"position":3,"is_corresponding":false},{"id":749395,"name":"Norihiro Matsuura","orcid":"0000-0001-8956-4600","position":4,"is_corresponding":false},{"id":663459,"name":"Samuel Flashner","orcid":"0000-0001-9796-0515","position":5,"is_corresponding":false},{"id":1281305,"name":"Mesra S. Ebadi","orcid":null,"position":6,"is_corresponding":false},{"id":1281306,"name":"Emilea H. Okayasu","orcid":null,"position":7,"is_corresponding":false},{"id":1281307,"name":"Christian Y. Lee","orcid":null,"position":8,"is_corresponding":false},{"id":279638,"name":"William Britton","orcid":"0000-0001-6778-3693","position":9,"is_corresponding":false},{"id":340214,"name":"Cecilia Martin","orcid":"0000-0001-7096-986X","position":10,"is_corresponding":false},{"id":516218,"name":"Beverly R. Wuertz","orcid":"0000-0002-2583-9043","position":11,"is_corresponding":false},{"id":684915,"name":"Anuraag S. Parikh","orcid":"0000-0003-0968-1028","position":12,"is_corresponding":false},{"id":15999,"name":"Uma M. Sachdeva","orcid":"0000-0002-0442-3794","position":13,"is_corresponding":false},{"id":73870,"name":"Frank G. Ondrey","orcid":"0000-0002-4951-9335","position":14,"is_corresponding":false},{"id":453383,"name":"Venkatram R. Atigadda","orcid":"0000-0003-0085-0403","position":15,"is_corresponding":false},{"id":350477,"name":"Craig A. Elmets","orcid":"0000-0001-7131-4697","position":16,"is_corresponding":false},{"id":237786,"name":"Julian A. Abrams","orcid":"0000-0002-6021-9376","position":17,"is_corresponding":false},{"id":366510,"name":"Amanda B. Muir","orcid":"0000-0003-2616-7063","position":18,"is_corresponding":false},{"id":500947,"name":"Andres J. Klein–Szanto","orcid":"0000-0002-5533-9402","position":19,"is_corresponding":false},{"id":14913,"name":"Kenneth I. 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