High cardiomyocyte diversity in human early prenatal heart development

Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Here, we characterized human prenatal cardiomyocytes, 6.5-7 weeks post-conception, by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand-receptor crosstalk is mainly with non-cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location-dependent properties, with complex ligand-receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies.

Automated summary

Human prenatal cardiomyocytes were characterized using single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Eight types of developing cardiomyocytes were identified, more than double the ones in the Human Developmental Cell Atlas. These cells exhibit high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles and atria. The ligand-receptor crosstalk of cardiomyocytes is mainly with non-cardiomyocyte cell types and involves cardiogenesis-related pathways. Understanding the developmental dynamics of early prenatal human cardiomyocytes may lead to new therapies.