Identification of cell-to-cell interactions by ligand-receptor pairs in human fetal heart.

The heart is the first organ to form during embryogenesis and its development is a complex process. In this study, we identified 120 ligand-receptor pairs including 65 ligands and 58 receptors specifically expressed in one of the nine cell types. The correlation analysis of the cell proportions revealed that the cell-to-cell contact exhibited spatial patterns in human fetal heart. Specifically, the cardiomyocytes (CMs) proportion might have negative correlation with proportion of endothelial cell in left atrium and ventricle during the heart development. In contrast, fibroblast-like cells and macrophages were jointly increased with the gestation. Furthermore, the ligand in CM, NPPA (Natriuretic Peptide A), and receptor in endothelial cell (EC), NPR3 (Natriuretic Peptide Receptor 3), were specifically expressed in atrial CM and endocardial cells, respectively, indicating that the atrial CM might communicate with endocardial cells via NPPA-NRP3 interaction. Moreover, the interplay between fibroblast-like cell and macrophage was observed in both left and right atriums via the ligand-receptor interactions of COL1A1/COL1A2 (Collagen Type I Alpha 1/2 Chain)-CD36 and CTGF (connective tissue growth factor)-ITGB2 (Integrin Subunit Beta 2). Functional enrichment analysis revealed that the ligand-receptor interactions might be associated with the intracellular activation of cGMP-PKG signaling pathway in ECs, PDGF-beta signaling pathway in fibroblast-like cell, and Toll-like receptor signaling in macrophage, respectively. Collectively, the present study unveiled the potential cell-cell communication and underlying mechanism involved in cardiac development, which broadened our insights into developmental biology of heart.