Tiered sympathetic control of cardiac function revealed by viral tracing and single cell transcriptome profiling
- University of California, Los Angeles, United States
- University of California, San Francisco, United States
- University of California, San Diego, United States
- Alnylam Pharmaceuticals, United States
- Garvan Institute of Medical Research, Australia
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)
Article and author information
Author details
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).
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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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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