{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:06:09Z","timestamp":1791489969963,"version":"4.3.4"},"reference-count":72,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015629","name":"Jerome L. Greene Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100015629","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:p>\n                    The lacrimal gland is of central interest in ophthalmology both as the source of the aqueous component of tear fluid and as the site of autoimmune pathology in the context of Sjogren\u2019s syndrome (SjS). To provide a foundational description of mouse lacrimal gland cell types and their patterns of gene expression, we have analyzed single-cell transcriptomes from wild-type (Balb\/c) mice and from two genetically based SjS models,\n                    <jats:italic>MRL\/lpr<\/jats:italic>\n                    and\n                    <jats:italic>NOD<\/jats:italic>\n                    (nonobese diabetic)\n                    <jats:italic>.H2b<\/jats:italic>\n                    , and defined the localization of multiple cell-type-specific protein and mRNA markers. This analysis has uncovered a previously undescribed cell type, Car6+ cells, which are located at the junction of the acini and the connecting ducts. More than a dozen secreted polypeptides that are likely to be components of tear fluid are expressed by acinar cells and show pronounced sex differences in expression. Additional examples of gene expression heterogeneity within a single cell type were identified, including a gradient of Claudin4 along the length of the ductal system and cell-to-cell heterogeneity in transcription factor expression within acinar and myoepithelial cells. The patterns of expression of channels, transporters, and pumps in acinar, Car6+, and ductal cells make strong predictions regarding the mechanisms of water and electrolyte secretion. In\n                    <jats:italic>MRL\/lpr<\/jats:italic>\n                    and\n                    <jats:italic>NOD.H2b<\/jats:italic>\n                    lacrimal glands, distinctive changes in parenchymal gene expression and in immune cell subsets reveal widespread interferon responses, a T cell\u2013dominated infiltrate in the\n                    <jats:italic>MRL\/lpr<\/jats:italic>\n                    model, and a mixed B cell and T cell infiltrate in the\n                    <jats:italic>NOD.H2b<\/jats:italic>\n                    model.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2311983120","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T15:09:14Z","timestamp":1696864154000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Normal and Sjogren\u2019s syndrome models of the murine lacrimal gland studied at single-cell resolution"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-6212","authenticated-orcid":false,"given":"Amir","family":"Rattner","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"HHMI, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6291-6688","authenticated-orcid":false,"given":"Jacob S.","family":"Heng","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana L.","family":"Winer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-451X","authenticated-orcid":false,"given":"Loyal A.","family":"Goff","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Kavli Neurodiscovery Institute, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8106-5460","authenticated-orcid":false,"given":"Jeremy","family":"Nathans","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"HHMI, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"},{"name":"Wilmer Eye Institute, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00004-4"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000131066"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-0124(12)70222-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108115"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24551"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2018.07.023"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.197657"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1407936"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"16047","DOI":"10.1038\/nrdp.2016.47","article-title":"Sj\u00f6gren syndrome","volume":"2","author":"Brito-Zer\u00f3n P.","year":"2016","unstructured":"P. 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S. Heng Single-cell transcriptional landscape of the murine lacrimal gland in health and disease. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE132420. 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