Improving human cardiac organoid design using transcriptomics.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Organoid Technology

Background:

• Cardiovascular disease (CVD) remains a leading global cause of mortality.
• Human cardiac organoids (hCOs) are emerging as superior models for CVD research compared to traditional animal models.
• hCOs utilize human cells, offering insights into human-specific disease mechanisms.

Purpose of the Study:

• To investigate the heterogeneity and maturity of human cardiac organoids (hCOs) derived from different fabrication methods.
• To compare transcriptomic profiles of hCOs with 2D/3D cardiomyocytes and human heart tissues.
• To establish a link between hCO fabrication techniques and their resultant modeling potential.

Main Methods:

• Bulk RNA-sequencing was performed on hCOs from four distinct studies.
• Transcriptomic data was analyzed using Principal Component Analysis and K-means clustering.
• Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and Gene Ontology (GO) term enrichment were employed.

Main Results:

• Fabrication methods significantly influence the maturity and cellular heterogeneity of hCOs.
• Transcriptomic profiles varied considerably across different hCO platforms.
• Distinct hCO models showed unique gene expression patterns compared to 2D/3D cardiomyocytes and human myocardium.

Conclusions:

• The fabrication method is a critical determinant of hCO characteristics, including maturity and transcriptomic profile.
• Tailoring fabrication techniques can yield hCOs with specific, predictable profiles for targeted CVD modeling applications.
• Optimizing hCO fabrication maximizes their potential for advancing cardiovascular disease research.