Transcriptomics reveal stretched human pluripotent stem cell-derived cardiomyocytes as an advantageous hypertrophy...

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Molecular Cardiology

Background:

• Left ventricular hypertrophy is a cardiac response to increased workload, potentially leading to heart failure.
• Existing models using neonatal rat ventricular myocytes (NRVMs) and animal models have limitations in human applicability.
• Understanding human cardiomyocyte hypertrophy is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the effects of mechanical stretch on gene expression in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
• To identify novel genes and biological pathways involved in human cardiomyocyte hypertrophy.
• To establish hiPSC-CMs as a relevant in vitro model for studying human cardiac hypertrophy.

Main Methods:

• Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were subjected to cyclic mechanical stretch.
• RNA sequencing was employed to analyze global gene expression changes.
• Differential gene expression analysis was performed and compared with existing data from NRVMs and human embryonic stem cell-derived cardiomyocytes.

Main Results:

• hiPSC-CMs exhibited significant hypertrophic changes in gene expression, affecting individual genes and biological processes.
• Several novel differentially expressed genes associated with cardiomyocyte hypertrophy were identified.
• Compared to NRVMs, hiPSC-CMs showed fewer gene expression changes but more pronounced enrichment of hypertrophy-related pathways.

Conclusions:

• hiPSC-CMs represent a valuable and human-relevant in vitro model for studying cardiomyocyte hypertrophy.
• The identified novel genes offer potential therapeutic targets for conditions involving cardiac hypertrophy.
• This study advances the understanding of molecular mechanisms underlying human cardiac hypertrophy.