{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:30:42Z","timestamp":1792801842697,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>BRCA1 (breast cancer 1, early onset) is originally identified as a tumor suppressor in hereditary breast and ovarian cancer. Recent studies have suggested that BRCA1 contributes to the cell fate decisions in mammary epithelium. Although BRCA1 has been shown to be expressed in the thymus, its physiologic role(s) in the thymus remain unclear. In this study, we found that BRCA1 was expressed in a subset of thymic medullary epithelial cells: epithelial cell adhesion molecule (EpCAM, CD326) positive, UEA-1 ligand positive, and Aire negative. To clarify its functional significance, we analyzed the differentiation of thymic epithelial cells in mice in which BRCA1 was specifically deleted in K14-expressing cells. Interestingly, conditional BRCA1-deficient mice displayed enhanced development of Hassall\u2019s corpuscles. Notably, thymoproteasome catalytic subunit \u03b25t (proteasome subunit beta 11), a marker of cortical thymic epithelial cells (cTECs), was frequently detected adjacent to Hassall\u2019s corpuscles in BRCA1 knockout mice. In addition, medullary \u03b25t+ cells appeared to differentiate into cTECs. In addition, BRCA1 deficiency led to increased generation of regulatory T cells. Thus, BRCA1 was also found to regulate epithelial differentiation in the thymus. Our observations in BRCA1-deficient mice may be relevant to understanding the immune system in human with BRCA1 germline mutations.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf069","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:35:22Z","timestamp":1764938122000},"source":"Crossref","is-referenced-by-count":1,"title":["BRCA1 deficiency leads to aberrant epithelial differentiation in the thymus"],"prefix":"10.1093","volume":"9","author":[{"given":"Chikako","family":"Odaka","sequence":"first","affiliation":[{"name":"Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"van de Ven","sequence":"additional","affiliation":[{"name":"Preclinical Intervention Unit, Mouse Clinic for Cancer and Aging, The Netherlands Cancer Institute , Amsterdam,","place":["The 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Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Murata","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo , Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Blanpain","sequence":"additional","affiliation":[{"name":"Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universit\u00e9 Libre de Bruxelles , Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos","family":"Jonkers","sequence":"additional","affiliation":[{"name":"Oncode Institute and Division of Molecular Pathology, The Netherlands Cancer Institute , Amsterdam,","place":["The 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