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Vascularization of cardiac organoids controls the extracellular matrix environment and regulates organoid functionality

ABSTRACT: Crosstalk between cardiac cells is critical during heart development but its role in organ maturation is still largely uncharacterised. Here, we show that endothelial cells increase the force of contraction and enhance the expression of mature sarcomeric proteins and extracellular matrix (ECM) components in human pluripotent stem cell derived cardiac organoids (hCO). Endothelial cells regulate cardiac maturation and function both directly through secretion of ECM molecules and indirectly via paracrine signaling. Laminin α5, an endothelial enriched ECM protein, was identified as a key regulator of cardiac maturation and contractility in vitro. In vivo loss-of-function studies in mice confirmed that Lama5 was required for myocardial expansion during heart development in vivo. In addition, paracrine PDGF signaling was identified as a mediator of increased ECM deposition and cardiac contractility in hCO. This study uncovers matrix regulatory functions of endothelial cells governing cardiac maturation and highlights the importance of multicellularity for organoid models.

ORGANISM(S): Mus musculus

PROVIDER: GSE150998 | GEO | 2023/05/20

REPOSITORIES: GEO

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