High-resolution single-cell atlas of human and pig healthy heart reveals conserved and species-specific features

Cardiovascular disease is the leading cause of mortality worldwide, and pigs are a relevant large-animal model for human heart biology and xenotransplantation. To investigate cross-species cellular functional compatibility, we generated a single-cell and single-nucleus transcriptomic atlas from 14 cardiovascular regions of healthy Bama Xiang pigs, Large White pigs, and human hearts. We identified 15 major cell types with broad conservation across species, and further identified conserved cell–cell interactions. Comparative analysis revealed distinct vascular features: human cells upregulated antioxidant and cholesterol metabolism pathways, whereas porcine cells expressed APOA1, which is linked to reverse cholesterol transport. Additional differences were observed in the energy metabolism and electrophysiological profiles of cardiomyocytes, including the predominance of ATP1A1 and ATP1A2 in distinct species. Cross-species analysis of four species uncovered shared transcriptional programs and key regulators underlying cardiac cell identities. This comprehensive atlas provides a valuable resource for understanding cardiovascular biology and may help inform studies on pig-to-human heart xenotransplantation.