A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
Alison Moss,
Shaina Robbins,
Sirisha Achanta,
Lakshmi Kuttippurathu,
Scott Turick,
Sean Nieves,
Peter Hanna,
Elizabeth H. Smith,
Donald B. Hoover,
Jin Chen,
Zixi (Jack) Cheng,
Jeffrey L. Ardell,
Kalyanam Shivkumar,
James S. Schwaber,
Rajanikanth Vadigepalli
Affiliations
Alison Moss
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Shaina Robbins
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Sirisha Achanta
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Lakshmi Kuttippurathu
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Scott Turick
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Sean Nieves
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Peter Hanna
University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA, USA
Elizabeth H. Smith
Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
Donald B. Hoover
Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
Jin Chen
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA
Zixi (Jack) Cheng
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA
Jeffrey L. Ardell
University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA, USA
Kalyanam Shivkumar
University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA, USA; Corresponding author
James S. Schwaber
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Corresponding author
Rajanikanth Vadigepalli
Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Corresponding author
Summary: 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.
