Multi-Omics Characterization of a Human Stem Cell-Based Model of Cardiac Hypertrophy
Markus Johansson1,2, Benjamin Ulfenborg1, Christian X Andersson3
1Systems Biology Research Center, School of Bioscience, University of Skövde, SE-541 28 Skövde, Sweden.
Insights
Researchers developed a human induced pluripotent stem cell model to study cardiac hypertrophy. This model identified early biomarkers for cardiac hypertrophy, offering new insights into its mechanisms and potential clinical applications.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Molecular Cardiology
Background:
- Cardiac hypertrophy is a significant risk factor for cardiac myopathy and heart failure.
- The underlying mechanisms of cardiac hypertrophy progression remain incompletely understood.
- Developing robust in vitro models is crucial for studying cardiac hypertrophy.
Purpose of the Study:
- To establish and characterize a human induced pluripotent stem cell (hiPSC)-based in vitro model for cardiac hypertrophy.
- To investigate the molecular mechanisms and regulatory pathways involved in cardiac hypertrophy progression.
- To identify novel early biomarkers for cardiac hypertrophy using a multi-omics approach.
Main Methods:
- Generation of hiPSC-derived cardiomyocytes.
- Stimulation of cardiomyocytes with Endothelin-1 over 8, 24, 48, and 72 hours.
- Comprehensive characterization using transcriptomic and secreted proteome analysis (multi-omics).
Main Results:
- The hiPSC model demonstrated a clear hypertrophic response at both transcriptomic and secreted proteomic levels.
- Early identification of enriched canonical pathways associated with cardiac hypertrophy signaling.
- Integrated transcriptome-secretome analysis revealed multimodal biomarkers for early cardiac hypertrophy detection.
Conclusions:
- The developed hiPSC-based in vitro model effectively recapitulates cardiac hypertrophy.
- Novel insights into the mechanisms driving cardiac hypertrophy progression were obtained.
- Putative early cardiac hypertrophy biomarkers were identified, warranting further clinical investigation.
Abstract:
Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. The mechanisms underlying the development of cardiac hypertrophy are yet not well understood. To increase the knowledge about mechanisms and regulatory pathways involved in the progression of cardiac hypertrophy, we have developed a human induced pluripotent stem cell (hiPSC)-based in vitro model of cardiac hypertrophy and performed extensive characterization using a multi-omics approach. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48, and 72 h, and their transcriptome and secreted proteome were analyzed. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling. An integrated transcriptome-secretome analysis enabled the identification of multimodal biomarkers that may prove highly relevant for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on both transcriptomic- and secreted-proteomic levels. The results also shed novel insights into the underlying mechanisms of cardiac hypertrophy, and novel putative early cardiac hypertrophy biomarkers have been identified that warrant further investigation to assess their potential clinical relevance.
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