High-Content Imaging Approaches for Studying Single-Cardiomyocyte Pleiotropic Decision-Making

Cardiomyocyte hypertrophy and apoptosis underlie cardiomyopathies and heart failure. While previous studies have described hypertrophy or apoptosis at the level of cell populations, how individual cells commit to these distinct yet co-regulated fates is unclear. We used high-content imaging to track single-cell hypertrophy and apoptosis dynamics, revealing new features and unique subpopulation responses. Catecholamines isoproterenol and norepinephrine induced heterogeneous analog hypertrophy and digital apoptosis, which support a “grow and/or die” conceptual model for cell decisions. Multinomial log-linear models revealed that a cell’s initial size and DNA content predict its susceptibility to hypertrophy and apoptosis. This work integrates dynamic morphological and biochemical cell profiling to reveal that despite co-regulation, a cardiomyocyte’s decision to hypertrophy enhances survival.