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Previous studies have provided insights into the cell lineage relationships during tissue morphogenesis. However, little is known about the cell types composing the adult LG and their progenitors. Using scRNAseq, we established the first comprehensive cell atlas of the adult mouse LG to investigate the cell hierarchy, its secretory repertoire, and the sex differences. Our analysis uncovered the complexity of the stromal landscape. Epithelium subclustering revealed myoepithelial cells, acinar subsets, and two novel acinar subpopulations: Tfrchi and Car6hi cells. The ductal compartment contained Wfdc2+ multilayered ducts and an Ltf+ cluster formed by luminal and intercalated duct cells. Kit+ progenitors were identified as: Krt14+ basal ductal cells, Aldh1a1+ cells of Ltf+ ducts, and Sox10+ cells of the Car6hi acinar and Ltf+ epithelial clusters. Lineage tracing experiments revealed that the Sox10+ adult populations contribute to the myoepithelial, acinar, and ductal lineages. Using scRNAseq data, we found that the postnatally developing LG epithelium harbored key features of putative adult progenitors. Finally, we showed that acinar cells produce most of the sex-biased lipocalins and secretoglobins detected in mouse tears. Our study provides a wealth of new data on LG maintenance and identifies the cellular origin of sex-biased tear components.<\/jats:p>","DOI":"10.3390\/cells12101435","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T01:31:46Z","timestamp":1684719106000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The First Transcriptomic Atlas of the Adult Lacrimal Gland Reveals Epithelial Complexity and Identifies Novel Progenitor Cells in Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-9698","authenticated-orcid":false,"given":"Vanessa","family":"Delcroix","sequence":"first","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4421-5025","authenticated-orcid":false,"given":"Olivier","family":"Mauduit","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"},{"name":"Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8977-1834","authenticated-orcid":false,"given":"Takeshi","family":"Umazume","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Knox","sequence":"additional","affiliation":[{"name":"Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA"},{"name":"Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-5494","authenticated-orcid":false,"given":"Cintia S.","family":"de Paiva","sequence":"additional","affiliation":[{"name":"The Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlene A.","family":"Dartt","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-0444","authenticated-orcid":false,"given":"Helen P.","family":"Makarenkova","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0074-7696(06)49005-7","article-title":"Cell and molecular biology of human lacrimal gland and nasolacrimal duct mucins","volume":"249","author":"Paulsen","year":"2006","journal-title":"Int. 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