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It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> mutations. However, the molecular changes underlying malignant transformation remain unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 <jats:italic>BRCA1<\/jats:italic> germline mutation carriers (<jats:italic>BRCA1<\/jats:italic> carriers) and 3 normal controls with no high-risk history (non-<jats:italic>BRCA1<\/jats:italic> carriers).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Exploring the transcriptomes of 19,008 cells, predominantly from <jats:italic>BRCA1<\/jats:italic><jats:sup>+<\/jats:sup> samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of <jats:italic>BRCA1<\/jats:italic><jats:sup>+<\/jats:sup> samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one <jats:italic>BRCA1<\/jats:italic> carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8<jats:sup>+<\/jats:sup> T cell population from <jats:italic>BRCA1<\/jats:italic><jats:sup>+<\/jats:sup> carriers. Among those clonally expanded CD8<jats:sup>+<\/jats:sup> T cells, PD-1 was significantly increased in tubal mucosae of <jats:italic>BRCA1<\/jats:italic><jats:sup>+<\/jats:sup> patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with <jats:italic>BRCA1<\/jats:italic> germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with <jats:italic>BRCA1<\/jats:italic> germline mutation present with early development and rapid dissemination of HGSC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12916-022-02489-9","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:03:06Z","timestamp":1662681786000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dissection of transcriptome dysregulation and immune characterization in women with germline BRCA1 mutation at single-cell resolution"],"prefix":"10.1186","volume":"20","author":[{"given":"Xuexin","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanrun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Spirtos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ci Ci","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setsuko K.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanthi","family":"Lea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"issue":"1","key":"2489_CR1","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/s41467-017-00962-1","volume":"8","author":"SI Labidi-Galy","year":"2017","unstructured":"Labidi-Galy SI, Papp E, Hallberg D, Niknafs N, Adleff V, Noe M, et al. 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