Kinemomics: spatiotemporal morphodynamic mapping of ventricular kinematic subpopulations in organotypic fetal heart slices

Abstract

Recent advancements in omics technologies have deepened our understanding of complex biological systems and the interplay among gene expression, mechanical cues, and cellular metabolism. However, capturing the spatiotemporal dynamics of live cellular behavior within intact tissue contexts remains a major challenge. Here, we introduce Kinemomics, a framework for spatiotemporal mapping of morphogenetic kinematic states in living tissue. Using a novel fetal cardiac organotypic slice culture system that preserves both beating and morphogenesis, Kinemomics integrates live fluorescent labeling, timelapse imaging, and endpoint immunofluorescence to generate morphodynamic profiles across full-thickness developing myocardium. We validate Kinemomics under controlled Yap-1 signaling perturbations and demonstrate its ability not only to intrinsically decode region- and treatment-specific phenotypes, but also to resolve their spatiotemporal evolution during development and malformation. Kinemomics further reveals localized emergent developmental and malforming fronts that drive system-level behavior, establishing a generalizable platform for investigating computational morphodynamics and cross-scale interactions in complex spatiotemporal systems.