Effect of the Mutated p.H222P A-type Lamins on Gene Expression in Both Patient-Derived Cardiomyocytes and Mouse Models of Dilated Cardiomyopathy
Mutation on A-type lamins encoding gene can lead to a wide-range of diseases called laminopathies, including dilated cardiomyopathy. Nuclear lamins are integral to a physical continuum connecting the extracellular environment and the nuclear interior, playing a crucial role in load-bearing tissues like  the heart to preserve mechanical integrity and genome stability. To investigate the impact of the LMNA p.H222P mutation on gene expression, we conducteed bulk RNA-seq in hiPSCs-derived cardiomyocytes and mouse cardiomyocytes, both carrying this mutation. Our results reveal that the LMNA p.H222P mutation leads to dysregulated gene expression, which may contribute to LMNA cardiomyopathy pathogenesis. Overall design: bulk RNA-seq in hiPSCs-CMs (isogenic control and LMNA p.H222P cell lines) and heart sections from Lmna p.H222P/H222P and WT mice