A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system

We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion, the right atrial ganglionic plexus (RAGP) that is a critical mediator of sinoatrial node (SAN) activity. This 3D representation of RAGP used neuronal tracing to extensively map the spatial distribution of the subset of neurons that project to the SAN. RNA-seq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to the central nervous system and a surprising finding that cholinergic and catecholaminergic markers are coexpressed, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. High-throughput qPCR of hundreds of laser capture microdissected single neurons confirmed these findings and revealed a high dimensionality of neuromodulatory factors that contribute to dynamic control of the heart. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.

Automated summary

Through 3D neuronal tracing and RNA-seq technology, researchers have identified the unique composition and multipotential phenotypes of neurons in the right atrial ganglionic plexus (RAGP). These findings reveal a high dimensionality of neuromodulatory factors and a coexpression network of neuropeptide receptors within RAGP, providing new insights into neuroplasticity and cardiac function regulation.