Decoding Cardiac Development and Maturation at Single-Cell and Spatial Transcriptomic Resolution

Recent advances in single-cell transcriptomics have revolutionized our understanding of cardiac development and maturation by resolving cellular heterogeneity, delineating lineage trajectories, and uncovering gene regulatory networks and intercellular signaling at unprecedented resolution. The heart develops through a tightly coordinated spatiotemporal process that extends from early organogenesis through postnatal maturation. Despite major progress, key questions remain unresolved, including the localization and function of rare progenitor populations and the mechanisms that guide cardiomyocyte maturation and loss of regenerative capacity. Spatial transcriptomics has emerged as a powerful complement to single-cell profiling because it preserves the native tissue architecture and reveals how gene expression is organized within anatomic context. Although many spatial studies to date have focused on cardiac disease and injury, emerging developmental data sets spanning embryonic to postnatal stages now enable reconstruction of spatially resolved trajectories of heart formation. Here, we review key findings and limitations from recent single-cell and spatial transcriptomic studies of heart development and maturation and discuss how integrative approaches and advanced computational tools are redefining the molecular and spatial logic of cardiogenesis. These insights are expected to greatly accelerate future regenerative and translational research.