CGPO spatial transcriptomics data

Sinoatrial node (SAN), the principal pacemaker of the human heart, regulates cardiac rhythm under neural control. The SAN comprises a complex cellular ecosystem requiring precise spatiotemporal development, and its dysfunction leads to arrhythmias. However, due to the scarcity of human samples and robust in vitro organoid models, the spatial heterogeneity and cellular crosstalk during the developmental process of human SAN remain unclear. Here, we integrated organoid models and human embryonic SAN spatial omics to define human-specific features of SAN development and functional maturation. We firstly constructed differentiation systems for human functional SAN organoids (SANOs) and cardiac ganglion plexus organoids (CGPOs), simulating the crosstalks between the cardiac ganglion plexus and SAN pacemaker cells (SANPCs) within CGPO-SANO assembloids. These assembloids displayed similar cellular composition and neural innervation functions to the human embryonic SAN region. High-resolution spatial transcriptomic profiles of the SAN from a 12 -week post-conception human embryo revealed mutiple cellular crosstalk pathways between neurons and SANPCs, including PSAP-GPR37 axis, which is specificlly emerged in human embryonic stage. Interestingly, CGPO-SANO assembloids revealed that neurons secreted PSAP to promote the functional maturation of human SANPCs. Together, this study integrates spatial transcriptomics, human tissues and organoid models to outline the spatiotemporal dynamics of cellular communities in human SAN during developmental stage, revealing the significant role and regulatory mechanisms of cardiac ganglion plexus in heart rate orchestrate and human SAN development.