HiPS-Endothelial Cells Acquire Cardiac Endothelial Phenotype in Co-culture With hiPS-Cardiomyocytes
Emmi Helle1,2, Minna Ampuja1, Alexandra Dainis3
1Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Insights
Human induced pluripotent stem cells reveal crucial cardiac endothelial cell and cardiomyocyte communication. Co-culture promotes vascular and cardiac development, highlighting essential cell-cell interactions for heart growth.
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.
Abstract:
Cell-cell interactions are crucial for organ development and function. In the heart, endothelial cells engage in bidirectional communication with cardiomyocytes regulating cardiac development and growth. We aimed to elucidate the organotypic development of cardiac endothelial cells and cardiomyocyte and endothelial cell crosstalk using human induced pluripotent stem cells (hiPSC). Single-cell RNA sequencing was performed with hiPSC-derived cardiomyocytes (hiPS-CMs) and endothelial cells (hiPS-ECs) in mono- and co-culture. The presence of hiPS-CMs led to increased expression of transcripts related to vascular development and maturation, cardiac development, as well as cardiac endothelial cell and endocardium-specific genes in hiPS-ECs. Interestingly, co-culture induced the expression of cardiomyocyte myofibrillar genes and MYL7 and MYL4 protein expression was detected in hiPS-ECs. Major regulators of BMP- and Notch-signaling pathways were induced in both cell types in co-culture. These results reflect the findings from animal studies and extend them to human endothelial cells, demonstrating the importance of EC-CM interactions during development.
