{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:45:36Z","timestamp":1786589136843,"version":"build-2736575974"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1165890","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:57:26Z","timestamp":1678168646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism"],"prefix":"10.3389","volume":"14","author":[{"given":"Shuai","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoqi","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xigong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xieyuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.104","article-title":"Primary hyperparathyroidism","volume":"14","author":"Walker","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.050910","article-title":"Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: An update on the changing epidemiology of the disease","volume":"21","author":"Wermers","year":"2006","journal-title":"J Bone Miner Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2013.06.051","article-title":"The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record","volume":"154","author":"Press","year":"2013","journal-title":"Surgery"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4022","article-title":"Incidence and prevalence of primary hyperparathyroidism in a racially mixed population","volume":"98","author":"Yeh","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-007-9427-2","article-title":"Age- and sex-related incidence of surgically treated primary hyperparathyroidism","volume":"32","author":"Miller","year":"2008","journal-title":"World J Surg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-012-2378-3","article-title":"The role of gender in primary hyperparathyroidism: same disease, different presentation","volume":"19","author":"Mazeh","year":"2012","journal-title":"Ann Surg Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-002-6621-0","article-title":"Primary hyperparathyroidism revisited in menopausal women with serum calcium in the upper normal range at population-based screening 8 years ago","volume":"26","author":"Lundgren","year":"2002","journal-title":"World J Surg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01080","article-title":"Sex difference in the clinical presentation of primary hyperparathyroidism: Influence of menopausal status","volume":"102","author":"Castellano","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2964","DOI":"10.3390\/ijms21082964","article-title":"Gender predilection in sporadic parathyroid adenomas","volume":"21","author":"Yavropoulou","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e694","DOI":"10.1002\/ctm2.694","article-title":"Single-cell RNA sequencing technologies and applications: A brief overview","volume":"12","author":"Jovic","year":"2022","journal-title":"Clin Transl Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0071-8","article-title":"Single-cell RNA sequencing technologies and bioinformatics pipelines","volume":"50","author":"Hwang","year":"2018","journal-title":"Exp Mol Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/cco.0000000000000613","article-title":"Single-cell sequencing in hematology","volume":"32","author":"Brierley","year":"2020","journal-title":"Curr Opin Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s13046-021-01874-1","article-title":"Single-cell RNA sequencing in cancer research","volume":"40","author":"Zhang","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.04.006","article-title":"Single-cell RNA sequencing: Unraveling the brain one cell at a time","volume":"23","author":"Ofengeim","year":"2017","journal-title":"Trends Mol Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319742111","article-title":"Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia","volume":"111","author":"Shi","year":"2014","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00534-0","article-title":"Tutorial: guidelines for annotating single-cell transcriptomic maps using automated and manual methods","volume":"16","author":"Clarke","year":"2021","journal-title":"Nat Protoc"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B19","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.043","article-title":"UCell: Robust and scalable single-cell gene signature scoring","volume":"19","author":"Andreatta","year":"2021","journal-title":"Comput Struct Biotechnol J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa802","article-title":"Stable gene expression for normalisation and single-sample scoring","volume":"48","author":"Bhuva","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat Methods"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.11.069","article-title":"Parathyroid hormone and parathyroid hormone-related peptide, and their receptors","volume":"328","author":"Gensure","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.14670\/hh-17.179","article-title":"Expression of parathyroid hormone-related protein (PTHrP) in parathyroid tissue under normal and pathological conditions","volume":"17","author":"Kitazawa","year":"2002","journal-title":"Histol Histopathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3366","article-title":"Differential gene expression by oxyphil and chief cells of human parathyroid glands","volume":"97","author":"Ritter","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.12-4-333","article-title":"Hyperparathyroidism in chronic kidney disease: complexities within the commonplace","volume":"12","author":"Cai","year":"2012","journal-title":"Clin Med (Lond)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1165890\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:57:30Z","timestamp":1678168650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1165890\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":29,"alternative-id":["10.3389\/fendo.2023.1165890"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1165890","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"article-number":"1165890"}}