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Updated: May 11, 2026
Isolation and Cryopreservation of Neonatal Rat Cardiomyocytes
Published on: April 9, 2015
Single-cell dynamics reveal a stress-induced decision between hypertrophy and apoptosis in neonatal rat
Bryan Chun1, Lavie Ngo1, Jeffrey J Saucerman1
1Department of Biomedical Engineering, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA.
Insights
Cardiomyocyte hypertrophy and apoptosis are key to heart failure. This study reveals individual heart cells make an early "grow-or-die" decision, influencing disease progression.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Molecular Medicine
Background:
- Cardiomyocyte hypertrophy and apoptosis are central to cardiomyopathies and heart failure.
- Understanding individual cell fate decisions (growth vs. death) is crucial but remains unclear at the population level.
Purpose of the Study:
- To elucidate the single-cell decision-making processes underlying cardiomyocyte hypertrophy and apoptosis.
- To investigate the dynamics of cell growth and death in individual cardiomyocytes.
Main Methods:
- Developed a high-content microscopy approach for tracking single-cell dynamics in neonatal rat cardiomyocytes.
- Utilized staurosporine, phenylephrine, and isoproterenol treatments to induce specific cellular responses.
- Applied machine learning models to predict cell fate based on initial cellular characteristics.
Main Results:
- Significant single-cell variability in growth and death observed even in untreated cardiomyocytes.
- Specific treatments induced apoptosis or hypertrophy in subpopulations, not uniformly.
- Cells that underwent hypertrophy were protected from subsequent apoptosis, supporting a 'grow-or-die' model.
- Initial cell size and DNA content/condensation predicted cell fate bias.
Conclusions:
- Individual cardiomyocytes make an early commitment to either hypertrophy or apoptosis, supporting a 'grow-or-die' model.
- This single-cell profiling method clarifies how distinct cell fates arise from population-level observations.
- Early cell fate decisions in cardiomyocytes are critical determinants of cardiac health and disease.
Abstract:
Cardiomyocyte hypertrophy and apoptosis underlie cardiomyopathies and heart failure. While previous studies have reported both hypertrophy and apoptosis at the population level, how individual cells commit to these distinct analog and digital fates is unclear. To elucidate how individual cells decide to grow and/or die, we developed a high-content microscopy approach to track single-cell dynamics of neonatal rat cardiomyocytes. Even untreated cells exhibited substantial single-cell variability in growth and death. Uniform treatments of staurosporine or phenylephrine induced distinctive morphological programs resulting in apoptosis and hypertrophy, respectively, but only in cell subpopulations. Increasing concentrations of the β-adrenergic receptor agonist isoproterenol caused a population-level biphasic induction of hypertrophy and then apoptosis, consistent with either apoptosis in the most hypertrophic cells (a grow-and-die model) or an early decision between hypertrophy and delayed apoptosis (a grow-or-die model). By tracking single-cell fates, we found that when stressed with either isoproterenol or phenylephrine, individual cells that hypertrophy are protected from later apoptosis. Further, caspase 3 inhibition shifted the single-cell probability from apoptosis to hypertrophy fates. Machine learning models found that a cell's initial size and DNA content or condensation could predict a cell's bias for hypertrophy or apoptosis. Together, these data support a grow-or-die conceptual model for cardiomyocyte decisions. This single-cell profiling method for tracking joint analog-digital cell decisions reveals that despite hypertrophy and apoptosis co-occurring at the population level, individual cardiomyocytes decide early whether to grow or die.
