Single-cell and spatial transcriptomic technologies in cardiovascular development: Implications for congenital heart disease and regenerative medicine

Cardiac development constitutes a highly coordinated spatiotemporal process involving the precise regulation of numerous key genes and signaling pathways at specific anatomical sites and developmental stages. How distinct embryonic lineages coordinate with complex spatiotemporal microenvironments through cell fate transitions and the remodeling of developmental niches to regulate cardiac chamber specification, conduction system development, valvulogenesis, and vascular formation remains a fundamental question in understanding cardiovascular development. Elucidating these processes in greater depth is essential for understanding the mechanisms underlying congenital heart disease (CHD) and for advancing cardiac regenerative research. In recent years, advances in single-cell and spatial transcriptomic technologies have overcome traditional research bottlenecks, providing novel perspectives for elucidating cardiovascular cell heterogeneity, lineage relationships, developmental trajectories, and cell-cell interactions. This review systematically summarizes recent advances in the application of single-cell and spatial transcriptomic technologies in cardiovascular development research, focusing on the developmental characteristics of three major tissue compartments, namely the myocardium, endocardium, and epicardium, and further outlines their applications in elucidating the mechanisms of CHD and in the field of cardiac regeneration. In the future, the deep integration of single-cell and spatial transcriptomic technologies with lineage tracing and functional genomics is expected to further elucidate the regulatory mechanisms of cardiovascular development and advance precision diagnostics and regenerative therapeutic strategies for these diseases.