Single cell transcriptomic analysis of salivary epithelial cells reveals large-scale dysregulation in bitter taste dysfunction

Single cell transcriptomic analysis of salivary epithelial cells reveals large-scale dysregulation in bitter taste dysfunction | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Single cell transcriptomic analysis of salivary epithelial cells reveals large-scale dysregulation in bitter taste dysfunction Mythily Srinivasan, Shveta Jaishankar, David Schaeper, Sarath Chandra Janga This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7566640/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Taste dysfunction or dysgeusia is a frequent symptom associated with infections and systemic diseases, yet its cellular and molecular basis remains poorly understood. The COVID-19 pandemic provided a “natural experiment” opportunity to study dysgeusia due to its high prevalence in acute and long-COVID (LC). We investigated salivary epithelial cells (SECs) using single-cell RNA sequencing to elucidate molecular changes underlying taste dysfunction in LC. Functional enrichment analysis of SEC transcriptomes from individuals with bitter taste dysfuncton(LC-D) revealed downregulation of genes involved in cytoskeletal dynamics and taste cell–nerve synapse assembly. Further, specific Type II and III taste receptor genes, critical for bitter taste perception, were reduced. Microbial defense markers such as toll-like receptor (TLR)2 and TLR4, were also downregulated, suggesting chronic inflammation. These findings support a model of sustained dysregulated epithelial turnover for the impaired taste in LC-D. Saliva-based single-cell approaches offer promising tools for future diagnostics and mechanistic studies of taste systems. Health sciences/Diseases/Oral diseases Health sciences/Signs and symptoms/Oral manifestations Full Text Additional Declarations There is no conflict of interest Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7566640","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":513349200,"identity":"022f50bd-0537-49aa-bf58-b392fc1f94a4","order_by":0,"name":"Mythily Srinivasan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYLCCBAYJBn5mEIuNFC2SzSRpAQGDA8Rq0Z2R/uzDwx0WiZuP8xgwfCg7TFiL2Y0c4xmJZyQStx3mMWCccY44LcwMiW0SxmZALcy8bURpSX8M1mLcDNTylzgtCcYgLXIGzEAtjERpOfMGokXiMFvBwZ5z6URoOZ7+mPFnWx0Pf//hjQ9+lFkT1sIgkIBgHyBCPRDwE6luFIyCUTAKRjAAAIoMNfaElmDhAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-1431-8215","institution":"Indiana Univ, Sch Dent, Dept Oral Pathol Med \u0026 Radiol, 1121 W Michigan St, Indianapolis, IN 46202 USA","correspondingAuthor":true,"prefix":"","firstName":"Mythily","middleName":"","lastName":"Srinivasan","suffix":""},{"id":513349201,"identity":"5a3ca1ed-d482-42a0-b3ad-17714606e560","order_by":1,"name":"Shveta Jaishankar","email":"","orcid":"","institution":"Indiana Univ, Sch Dent,","correspondingAuthor":false,"prefix":"","firstName":"Shveta","middleName":"","lastName":"Jaishankar","suffix":""},{"id":513349202,"identity":"3f311fe6-bb7c-4027-bfa8-9c1e9b3c18f4","order_by":2,"name":"David Schaeper","email":"","orcid":"","institution":"Department of Biomedical Engineering and Informatics, Luddy School of Informatics,","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Schaeper","suffix":""},{"id":513349203,"identity":"451a6187-eaa4-4cce-978c-72d5ead94164","order_by":3,"name":"Sarath Chandra Janga","email":"","orcid":"","institution":"Department of Biomedical Engineering and Informatics, Luddy School of Informatics,","correspondingAuthor":false,"prefix":"","firstName":"Sarath","middleName":"Chandra","lastName":"Janga","suffix":""}],"badges":[],"createdAt":"2025-09-08 17:25:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7566640/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7566640/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91384520,"identity":"f50d0974-6763-4279-bdb0-55aa5316a870","added_by":"auto","created_at":"2025-09-16 02:03:22","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2288635,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Srinivasanetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7566640/v1_covered_d2de229a-910e-4279-9b68-7efd62f762b4.pdf"}],"financialInterests":"There is no conflict of interest","formattedTitle":"\u003cp\u003eSingle cell transcriptomic analysis of salivary epithelial cells reveals large-scale dysregulation in bitter taste dysfunction\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7566640/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7566640/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Taste dysfunction or dysgeusia is a frequent symptom associated with infections and systemic diseases, yet its cellular and molecular basis remains poorly understood. 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