{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(15)"],"submitter":["Yamada S"],"pubmed_abstract":["Mutations in the <i>LMNA</i> 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<i>-LMNA-</i>related DCM. Inhibition of the Hippo pathway rescued the dysregulation of cardiac developmental genes by TEAD1 in <i>LMNA</i> mutant cardiomyocytes. Single-cell RNA-seq of cardiac tissues from patients with DCM with the <i>LMNA</i> mutation confirmed the dysregulated expression of TEAD1 target genes. Our results propose an intervention for transcriptional dysregulation as a potential treatment of <i>LMNA</i>-related DCM."],"journal":["Science advances"],"pagination":["eade7047"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10104473"],"repository":["biostudies-literature"],"pubmed_title":["TEAD1 trapping by the Q353R-Lamin A/C causes dilated cardiomyopathy."],"pmcid":["PMC10104473"],"pubmed_authors":["Hamano M","Kikkawa S","Ito M","Kubota M","Umezawa A","Katoh M","Morita H","Ko T","Imasaki T","Zhang B","Katagiri M","Ikeuchi M","Toyoda M","Komuro I","Takeda N","Hatsuse S","Yamada T","Yamada S","Aburatani H","Takada S","Seki Y","Fujita K","Sassa T","Okuma H","Nitta R","Hayashi H","Sato M","Yamanishi Y","Nomura S","Uchiyama M","Toyooka K"],"additional_accession":[]},"is_claimable":false,"name":"TEAD1 trapping by the Q353R-Lamin A/C causes dilated cardiomyopathy.","description":"Mutations in the <i>LMNA</i> 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<i>-LMNA-</i>related DCM. Inhibition of the Hippo pathway rescued the dysregulation of cardiac developmental genes by TEAD1 in <i>LMNA</i> mutant cardiomyocytes. Single-cell RNA-seq of cardiac tissues from patients with DCM with the <i>LMNA</i> mutation confirmed the dysregulated expression of TEAD1 target genes. Our results propose an intervention for transcriptional dysregulation as a potential treatment of <i>LMNA</i>-related DCM.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2025-04-18T14:52:04.36Z","creation":"2025-02-18T23:26:22.815Z"},"accession":"S-EPMC10104473","cross_references":{"pubmed":["37058558"],"doi":["10.1126/sciadv.ade7047"]}}