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This study aimed to define TC structure in mice submandibular glands (SMGs), determine how TC loss affects gland organization and function, and evaluate whether TC abundance in human minor SGs is associated with Sj\u00f6gren\u2019s disease (SjD) features. Specifically, TC ultrastructure and ductal localization were characterized in female and male C57BL\/6J mouse SMGs by transmission electron microscopy and immunostaining. Wild-type and C57BL\/6J-Pou2f3-\/- (TC-deficient mouse strain) SMGs were analyzed by histology and bulk RNA-seq, and salivary function was assessed by saliva flow and proteomics. Human minor SG biopsies from SjD and non-Sj\u00f6gren sicca (nSjD) patients were analyzed by immunostaining and Poisson regression. In mice SMGs, TCs showed conserved ultrastructural features and localization in both sexes. TC loss was associated with marked sex-biased transcriptome remodeling, morphological disruption, and altered saliva quantity and quality. In humans, TC counts differed between nSjD and SjD groups and were associated with salivary flow, serologic status, and histopathologic features. These findings support a role for TCs in SG epithelial integrity and suggest TC abundance as a candidate biomarker of SG dysfunction.<\/jats:p>","DOI":"10.3390\/cells15070583","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T13:57:34Z","timestamp":1774447054000},"page":"583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Highlights of Tuft Cells in Mouse and Human Salivary Glands"],"prefix":"10.3390","volume":"15","author":[{"given":"Michael E.","family":"Rusiniak","sequence":"first","affiliation":[{"name":"Department of Oral Biology, The State University of New York at Buffalo, Buffalo, NY 14214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Shimagami","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, The State University of New York at Buffalo, Buffalo, NY 14214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Zanetti","family":"Drumond","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Oral Pathology and Clinical Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte 31270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8194-1425","authenticated-orcid":false,"given":"Mariana Silveira","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Oral Pathology and Clinical Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte 31270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Luiza Araujo Lima de","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Oral Pathology and Clinical Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte 31270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xue","sequence":"additional","affiliation":[{"name":"New York State Center of Excellence in Bioinformatics & Life Sciences, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"New York State Center of Excellence in Bioinformatics & Life Sciences, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1346-6809","authenticated-orcid":false,"given":"Jun","family":"Qu","sequence":"additional","affiliation":[{"name":"New York State Center of Excellence in Bioinformatics & Life Sciences, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Edward","family":"Chlipala","sequence":"additional","affiliation":[{"name":"Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Maienschein-Cline","sequence":"additional","affiliation":[{"name":"Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9623-7835","authenticated-orcid":false,"given":"Tarcilia Aparecida da","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Oral Pathology and Clinical Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte 31270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7820-4749","authenticated-orcid":false,"given":"Silvia Ferreira de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Oral Pathology and Clinical Dentistry, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte 31270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-6808","authenticated-orcid":false,"given":"Harim Tavares","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, The State University of New York at Buffalo, Buffalo, NY 14214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF00345847","article-title":"Electron microscopy of the tracheal ciliated mucosa in rat","volume":"44","author":"Rhodin","year":"1956","journal-title":"Z. 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