Integrating Spatial Omics and Deep Learning: Toward Predictive Models of Cardiomyocyte Differentiation Efficiency

Advances in cardiac regenerative medicine increasingly rely on integrating artificial intelligence with spatial multi-omics technologies to decipher intricate cellular dynamics in cardiomyocyte differentiation. This systematic review, synthetising insights from 88 PRISMA selected studies spanning 2015–2025, explores how deep learning architectures, specifically Graph Neural Networks (GNNs) and Recurrent Neural Networks (RNNs), synergise with multi-modal single-cell datasets, spatially resolved transcriptomics, and epigenomics to advance cardiac biology. Innovations in spatial omics technologies have revolutionised our understanding of the organisation of cardiac tissue, revealing novel cellular communities and metabolic landscapes that underlie cardiovascular health and disease. By synthesising cutting-edge methodologies and technical innovations across these 88 studies, this review establishes the foundation for AI-enabled cardiac regeneration, potentially accelerating the clinical adoption of regenerative treatments through improved therapeutic prediction models and mechanistic understanding. We examine deep learning implementations in spatiotemporal genomics, spatial multi-omics applications in cardiac tissues, cardiomyocyte differentiation challenges, and predictive modelling innovations that collectively advance precision cardiology and next-generation regenerative strategies.