{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:01:09Z","timestamp":1791576069277,"version":"4.3.4"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,4,14]]},"abstract":"<jats:p>\n            Mutations in the\n            <jats:italic>LMNA<\/jats:italic>\n            gene encoding Lamin A and C (Lamin A\/C), major components of the nuclear lamina, cause laminopathies including dilated cardiomyopathy (DCM), but the underlying molecular mechanisms have not been fully elucidated. Here, by leveraging single-cell RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), protein array, and electron microscopy analysis, we show that insufficient structural maturation of cardiomyocytes owing to trapping of transcription factor TEA domain transcription factor 1 (TEAD1) by mutant Lamin A\/C at the nuclear membrane underlies the pathogenesis of Q353R\n            <jats:italic>-LMNA\u2013<\/jats:italic>\n            related DCM. Inhibition of the Hippo pathway rescued the dysregulation of cardiac developmental genes by TEAD1 in\n            <jats:italic>LMNA<\/jats:italic>\n            mutant cardiomyocytes. Single-cell RNA-seq of cardiac tissues from patients with DCM with the\n            <jats:italic>LMNA<\/jats:italic>\n            mutation confirmed the dysregulated expression of TEAD1 target genes. Our results propose an intervention for transcriptional dysregulation as a potential treatment of\n            <jats:italic>LMNA<\/jats:italic>\n            -related DCM.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ade7047","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T17:58:17Z","timestamp":1681495097000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["TEAD1 trapping by the Q353R\u2013Lamin A\/C causes dilated cardiomyopathy"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-358X","authenticated-orcid":true,"given":"Shintaro","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."},{"name":"Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9043-064X","authenticated-orcid":true,"given":"Toshiyuki","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-3137","authenticated-orcid":true,"given":"Masamichi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."},{"name":"Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0286-7073","authenticated-orcid":true,"given":"Tatsuro","family":"Sassa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."},{"name":"Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2957-2016","authenticated-orcid":true,"given":"Seitaro","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."},{"name":"Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-0805","authenticated-orcid":true,"given":"Hiromichi","family":"Okuma","sequence":"additional","affiliation":[{"name":"Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-5612","authenticated-orcid":true,"given":"Mayuko","family":"Sato","sequence":"additional","affiliation":[{"name":"RIKEN Center for Sustainable Resource Science, Yokohama, Kanagawa 230-0045, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5462-1820","authenticated-orcid":true,"given":"Tsuyoshi","family":"Imasaki","sequence":"additional","affiliation":[{"name":"Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kikkawa","sequence":"additional","affiliation":[{"name":"Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-6985","authenticated-orcid":true,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."},{"name":"Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8258-4219","authenticated-orcid":true,"given":"Takanobu","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."},{"name":"Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Seki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0638-3121","authenticated-orcid":true,"given":"Kanna","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of 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Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-7682","authenticated-orcid":true,"given":"Satoshi","family":"Hatsuse","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-6619","authenticated-orcid":true,"given":"Mikako","family":"Katagiri","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8924-2943","authenticated-orcid":true,"given":"Hiromu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-7053","authenticated-orcid":true,"given":"Momoko","family":"Hamano","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-3347","authenticated-orcid":true,"given":"Norifumi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate 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