| First Author | Yamada S | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 15 | Pages | eade7047 |
| PubMed ID | 37058558 | Mgi Jnum | J:335522 |
| Mgi Id | MGI:7465837 | Doi | 10.1126/sciadv.ade7047 |
| Citation | Yamada S, et al. (2023) TEAD1 trapping by the Q353R-Lamin A/C causes dilated cardiomyopathy. Sci Adv 9(15):eade7047 |
| abstractText | Mutations in the LMNA 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-LMNA-related DCM. Inhibition of the Hippo pathway rescued the dysregulation of cardiac developmental genes by TEAD1 in LMNA mutant cardiomyocytes. Single-cell RNA-seq of cardiac tissues from patients with DCM with the LMNA mutation confirmed the dysregulated expression of TEAD1 target genes. Our results propose an intervention for transcriptional dysregulation as a potential treatment of LMNA-related DCM. |
