HiPS-Endothelial Cells Acquire Cardiac Endothelial Phenotype in Co-culture With hiPS-Cardiomyocytes

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Developmental Biology

Background:

• Cell-cell interactions are fundamental for organogenesis and function.
• Endothelial cells (ECs) and cardiomyocytes (CMs) communicate bidirectionally, influencing cardiac development and growth.

Purpose of the Study:

• To investigate the organotypic development of cardiac ECs and EC-CM crosstalk.
• To utilize human induced pluripotent stem cells (hiPSCs) for studying these interactions.

Main Methods:

• Single-cell RNA sequencing was employed on hiPSC-derived cardiomyocytes (hiPS-CMs) and endothelial cells (hiPS-ECs).
• Cells were cultured individually (mono-culture) and together (co-culture) to analyze gene expression changes.

Main Results:

• hiPS-CMs significantly upregulated ECs' vascular development, maturation, and cardiac-specific gene expression.
• Co-culture induced cardiomyocyte myofibrillar gene expression in hiPS-ECs, with MYL7 and MYL4 protein detected.
• Key regulators of BMP and Notch signaling pathways were activated in both cell types during co-culture.

Conclusions:

• Human induced pluripotent stem cell-derived ECs and CMs recapitulate key aspects of cardiac development interactions.
• EC-CM crosstalk is vital for cardiac development, as evidenced by gene and protein expression changes in hiPSC models.
• Findings in human cells align with and extend observations from animal studies on cardiac development signaling.