Lamin B1 loss in human cardiomyocytes is associated with nuclear shape deformation in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a progressive heart muscle disease characterized by the enlargement of the heart's left ventricle. The aetiology of the disease can be genetic and/or environmental. Mutations in LMNA, the gene encoding for the nuclear lamina protein lamin A/C, are associated with approximately 6% of DCM, however, the role of the functionally related lamin B1 remains unknown. Lamin B1 provides structural integrity to the nucleus and regulates gene expression by restricting the accessibility and transcription of lamin B1 tethered genes. Our study focuses on the lamin B1 content and nuclear shape in human DCM. We first compare the levels of lamin B1 expression at the protein level in non-failing versus DCM diagnosed human hearts and then use an unbiased immunofluorescence and morphological phenotyping approach of cardiomyocyte nuclei to classify subpopulations of cells. This revealed that hearts diagnosed with DCM show a higher prevalence of nuclei within cardiomyocytes that were deformed and had a loss of lamin B1 signal. Using our unbiased analysis of the cardiomyocyte nuclei, we can separate non-failing from DCM donors. In conclusion, our study shows that lamin B1 loss in human cardiomyocytes is associated with nuclear shape deformation in dilated cardiomyopathy.