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

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 d...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2021-07-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221006817
id doaj-ee23db1917214094b15a355b972b98d1
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
iScience
Cardiovascular medicine
Molecular physiology
Systems neuroscience
Transcriptomics
author_facet 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
author_sort Alison Moss
title A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
title_short A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
title_full A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
title_fullStr A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
title_full_unstemmed A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
title_sort single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2021-07-01
description 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.
topic Cardiovascular medicine
Molecular physiology
Systems neuroscience
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004221006817
work_keys_str_mv AT alisonmoss asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT shainarobbins asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT sirishaachanta asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT lakshmikuttippurathu asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT scottturick asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT seannieves asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT peterhanna asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT elizabethhsmith asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT donaldbhoover asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT jinchen asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT zixijackcheng asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT jeffreylardell asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT kalyanamshivkumar asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT jamessschwaber asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT rajanikanthvadigepalli asinglecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT alisonmoss singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT shainarobbins singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT sirishaachanta singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT lakshmikuttippurathu singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT scottturick singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT seannieves singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT peterhanna singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT elizabethhsmith singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT donaldbhoover singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT jinchen singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT zixijackcheng singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT jeffreylardell singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT kalyanamshivkumar singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT jamessschwaber singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
AT rajanikanthvadigepalli singlecelltranscriptomicsmapofparacrinenetworksintheintrinsiccardiacnervoussystem
_version_ 1721290574576746496
spelling doaj-ee23db1917214094b15a355b972b98d12021-07-23T04:50:17ZengElsevieriScience2589-00422021-07-01247102713A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous systemAlison Moss0Shaina Robbins1Sirisha Achanta2Lakshmi Kuttippurathu3Scott Turick4Sean Nieves5Peter Hanna6Elizabeth H. Smith7Donald B. Hoover8Jin Chen9Zixi (Jack) Cheng10Jeffrey L. Ardell11Kalyanam Shivkumar12James S. Schwaber13Rajanikanth Vadigepalli14Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USADaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USAUniversity of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA, USADepartment of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USADepartment of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USAUniversity of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA, USAUniversity of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA, USA; Corresponding authorDaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Corresponding authorDaniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221006817Cardiovascular medicineMolecular physiologySystems neuroscienceTranscriptomics