Roles of Neuromedin-U and Endothelin-1 in human cardiac organoid differentiation

NMU treatment in human cardiac organoid ventricular lineages shifts differentiation away from ventricular cardiomyocytes, increasing beating frequency, while having no effect in atrial cultures.

• Why it matters: Existing differentiation protocols miss additional developmentally relevant signaling pathways that could tune cardiomyocyte fate and electrophysiological maturation in organoids.
• What they did: Using a cardiac differentiation roadmap, the study tested NMU and endothelin 1 (ET-1, EDN1) signaling, measuring lineage outcomes with reporters and cell type-specific markers and assessing electrophysiology via beating frequency and action potential propagation.
• The result: ET-1 increased atrial cardiomyocytes and altered repolarization, contraction frequency, and action potential propagation patterns; in ventricular cultures, ET-1 reduced vCM numbers, suggesting a combinatorial effect with retinoic acid (RA).