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Tissue homeostasis requires coordinated actions of epithelial, mesenchymal, and immune cells. However, the extent of heterogeneity within the human oral mucosa and how tissue cell types are affected during the course of disease progression is unknown. Using single-cell transcriptome profiling we reveal a striking remodelling of the epithelial and mesenchymal niches with a decrease in functional populations that are linked to the aetiology of the disease. Analysis of ligand\u2013receptor interaction pairs identify potential intercellular hubs driving the inflammatory component of the disease. Our work establishes a reference map of the human oral mucosa in health and disease, and a framework for the development of new therapeutic strategies.<\/jats:p>","DOI":"10.7554\/elife.62810","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T10:01:19Z","timestamp":1609754479000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62810","source":"Crossref","is-referenced-by-count":117,"title":["Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4588-3241","authenticated-orcid":true,"given":"Ana J","family":"Caetano","sequence":"first","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London, London, United 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