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Size-Modulated Mesoderm-Endoderm Divergence and Myocardial Cavitation in Micropatterned Cardioids
Plansky Hoang1,2, David W McKellar3, Andrew Kowalczewski1,2
1Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 16, 2026
Summary
This study uses micropatterned cardioids to model early human heart and foregut development. It reveals crucial mesoderm-endoderm signaling pathways essential for organogenesis.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Organogenesis
Background:
- The human heart develops from splanchnic mesoderm, co-evolving with the foregut endoderm via signaling.
- Existing cardioid models provide insights into cardiovascular development, but mesoderm-endoderm crosstalk is not fully understood.
Purpose of the Study:
- To investigate synergistic mesoderm-endoderm co-development using advanced cardioid models.
- To elucidate the signaling interactions between cardiac and hepatic lineages during early embryogenesis.
Main Methods:
- Integration of micropatterned cardioids, CRISPR-engineered human induced pluripotent stem cells (hiPSCs), deep-tissue imaging, and single-cell RNA sequencing (scRNA-seq).
- PHATE trajectory mapping for lineage reconstruction and ligand-receptor interaction analysis to identify signaling pathways.
Main Results:
- Reconstructed lineage bifurcations for mesoderm-heart and endoderm-foregut development, identifying key cell types.
- Highlighted distinct signaling activities: mesodermal cells showed WNT, NRG, and TGF-β signaling; endodermal cells exhibited VEGF and Hedgehog activity.
- Micropattern size influenced cardioid cellular composition, cavitation, contractility, and signaling crosstalk, with 600 µm patterns promoting chamber-like formation.
Conclusions:
- Established micropatterned cardioids as a valuable model for studying mesoderm-endoderm co-development.
- Enhanced understanding of the synergistic relationship between heart and foregut development during early embryogenesis.
