Charting the cardiac landscape: Advances in spatial transcriptomics for heart biology.

The heart is the first organ to form in the developing embryo. Throughout development, it continues to grow and function to support the maturing fetus by circulating nutrients to all of the developing organs. Defects in the spatial organization of cardiac cells can lead to congenital heart defects (CHD), which affects 1-3 % of all live births, as well as adult heart diseases. Spatial transcriptomics has revolutionized our understanding of cardiac biology by providing high-resolution maps of gene expression within intact tissue, offering insights into cellular interactions and spatial organization across the entire heart. Recent improvements have enabled precise mapping of cellular heterogeneity within developing human hearts, revealing spatially organized populations of cardiomyocytes and non-cardiomyocyte cells and key signaling pathways in cardiac morphogenesis. Studies of adult hearts post-myocardial infarction (MI) using these technologies have unraveled gene expression patterns specific to injury zones. Furthermore, multi-modal approaches combining spatial transcriptomics with epigenetic, proteomic, and functional data have expanded our understanding of cell type-specific responses and molecular mechanisms underpinning cardiac injury responses and fibrosis. Here, we describe the range of spatial transcriptomic technologies currently available and discuss the technical considerations involved in conducting spatial analyses. We further highlight the progression from early spatial mapping techniques to contemporary high-resolution, multi-modal approaches in studying cardiac tissue, underscoring how these advancements provide unprecedented insights into heart development, disease, and regeneration, and discuss future directions for applying spatial transcriptomics to address fundamental questions in cardiovascular biology and therapy.