1. Medicine
  2. Neuroscience

Tiered sympathetic control of cardiac function revealed by viral tracing and single cell transcriptome profiling

  1. Sachin Sharma
  2. Russell Littman
  3. John D Tompkins
  4. Douglas Arneson
  5. Jaime Contreras
  6. Al-Hassan Dajani
  7. Kaitlyn Ang
  8. Amit Tsanhani
  9. Xin Sun
  10. Patrick Y Jay
  11. Herbert Herzog
  12. Xia Yang
  13. Olujimi A Ajijola  Is a corresponding author
  1. University of California, Los Angeles, United States
  2. University of California, San Francisco, United States
  3. University of California, San Diego, United States
  4. Alnylam Pharmaceuticals, United States
  5. Garvan Institute of Medical Research, Australia
https://doi.org/10.7554/eLife.86295
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Cite this article
  1. Sachin Sharma
  2. Russell Littman
  3. John D Tompkins
  4. Douglas Arneson
  5. Jaime Contreras
  6. Al-Hassan Dajani
  7. Kaitlyn Ang
  8. Amit Tsanhani
  9. Xin Sun
  10. Patrick Y Jay
  11. Herbert Herzog
  12. Xia Yang
  13. Olujimi A Ajijola
(2023)
Tiered sympathetic control of cardiac function revealed by viral tracing and single cell transcriptome profiling
eLife 12:e86295.
https://doi.org/10.7554/eLife.86295
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Abstract

The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) neuropeptide-Y (NPY) -expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.

Data availability

Data related to single-cell RNA seq analysis generated from this manuscript are available from the GEO database (GSE231924)

The following data sets were generated

Article and author information

Author details

  1. Sachin Sharma

    Neurocardiology Research Center of Excellence, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6776-1061

  2. Russell Littman

    Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.

  3. John D Tompkins

    Neurocardiology Research Center of Excellence, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9496-7930

  4. Douglas Arneson

    Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.

  5. Jaime Contreras

    Neurocardiology Research Center of Excellence, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.

  6. Al-Hassan Dajani

    Neurocardiology Research Center of Excellence, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.

  7. Kaitlyn Ang

    Neurocardiology Research Center of Excellence, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.

  8. Amit Tsanhani

    Neurocardiology Research Center of Excellence, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.

  9. Xin Sun

    Department of Pediatrics, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8387-4966

  10. Patrick Y Jay

    Alnylam Pharmaceuticals, Cambridge, United States
    Competing interests
    Patrick Y Jay, is affiliated with Alnylam Pharmaceuticals..

  11. Herbert Herzog

    Neuroscience Division, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1713-1029

  12. Xia Yang

    Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.

  13. Olujimi A Ajijola

    Cardiac Arrhythmia Center, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    OAjijola@mednet.ucla.edu
    Competing interests
    Olujimi A Ajijola, is a co-founder of NeuCures Inc.Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6197-7593

Funding

NIH Office of the Director (DP2HL142045)

  • Olujimi A Ajijola

NHLBI Division of Intramural Research (R01HL162717)

  • Olujimi A Ajijola

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experiments complied with institutional guidelines and ethical regulations, and the study protocol was approved by the UCLA institutional Animal Care and Use Committee. (protocol number: 18-048).

Reviewing Editor

  1. Christopher L-H Huang, University of Cambridge, United Kingdom

Publication history

  1. Preprint posted: January 19, 2023 (view preprint)
  2. Received: January 19, 2023
  3. Accepted: April 4, 2023
  4. Accepted Manuscript published: May 10, 2023 (version 1)
  5. Version of Record published: May 25, 2023 (version 2)

Copyright

© 2023, Sharma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sachin Sharma
  2. Russell Littman
  3. John D Tompkins
  4. Douglas Arneson
  5. Jaime Contreras
  6. Al-Hassan Dajani
  7. Kaitlyn Ang
  8. Amit Tsanhani
  9. Xin Sun
  10. Patrick Y Jay
  11. Herbert Herzog
  12. Xia Yang
  13. Olujimi A Ajijola
(2023)
Tiered sympathetic control of cardiac function revealed by viral tracing and single cell transcriptome profiling
eLife 12:e86295.
https://doi.org/10.7554/eLife.86295

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