Spatial transcriptomics reveals coordinated ventricular patterning and maturation in the developing human heart.

Abstract

Human heart development requires coordinated gene regulation across spatially organized tissues. However, the principles by which the heart establishes spatially organized structures and how regional programs integrate to orchestrate coordinated development remain unclear. Here, we generate a spatiotemporal transcriptomic atlas of the developing human hearts, profiling 30 sections spanning 8-15 post-conception weeks. By treating each spatial spot as a multicellular unit, we resolve anatomically coherent compartments and identify specialized subpopulations, including the Papillary muscle and Atrioventricular Plane. Focusing on the ventricle, trajectory inference reveals a continuous endocardium-to-epicardium transcriptional gradient, accompanied by coordinated changes in gene expression, transcription factor activity, and signaling pathways. Integrative developmental analysis identifies shared maturation-associated transcriptional changes, with increasing contractile and metabolic programs and declining proliferative signatures, alongside region-specific specialization across spatial domains. Together, this study defines a spatial framework for ventricular patterning and maturation, providing a resource for investigating human cardiac development and disease.