Pericytes control vascular stability and auditory spiral ganglion neuron survival

  1. Yunpei Zhang
  2. Lingling Neng
  3. Kushal Sharma
  4. Zhiqiang Hou
  5. Anatasiya Johnson
  6. Junha Song
  7. Alain Dabdoub
  8. Xiaorui Shi  Is a corresponding author
  1. Oregon Health & Science University, United States
  2. Lawrence Berkeley National Laboratory, United States
  3. Sunnybrook Research Institute, Canada

Abstract

The inner ear has a rich population of pericytes, a multi-functional mural cell essential for sensory hair cell heath and normal hearing. However, the mechanics of how pericytes contribute to the homeostasis of the auditory vascular-neuronal complex in the spiral ganglion is not yet known. In this study, using an inducible and conditional pericyte depletion mouse (PDGFRB-CreERT2; ROSA26iDTR) model, we demonstrate, for the first time, that pericyte depletion causes loss of vascular volume and spiral ganglion neurons (SGNs) and adversely affects hearing sensitivity. Using an in vitro trans-well co-culture system, we show pericytes markedly promote neurite and vascular branch growth in neonatal SGN explants and adult SGNs. The pericyte-controlled neural growth is strongly mediated by pericyte-released exosomes containing vascular endothelial growth factor-A (VEGF-A). Treatment of neonatal SGN explants or adult SGNs with pericyte-derived exosomes significantly enhances angiogenesis, SGN survival, and neurite growth, all of which were inhibited by a selective blocker of VEGF receptor 2 (Flk1). Our study demonstrates that pericytes in the adult ear are critical for vascular stability and SGN health. Cross-talk between pericytes and SGNs via exosomes is essential for neuronal and vascular health and normal hearing.

Data availability

Table 1 - Source Data 1 contains the RNA sequencing data used to generate Table 1 and Figure 5A. Figure 6 - Source Data 1 contains the proteomics data used to generate Figure 6 and Table 2. Figure 7 - Source Data 1 & 2 contains the original uncropped blots of VEGFA and PDGFR-β, and raw gel data of whole protein staining with the relevant bands clearly labelled.

Article and author information

Author details

  1. Yunpei Zhang

    Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5254-796X
  2. Lingling Neng

    Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kushal Sharma

    Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhiqiang Hou

    Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5154-7474
  5. Anatasiya Johnson

    Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Junha Song

    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Alain Dabdoub

    Biological Sciences, Sunnybrook Research Institute, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4259-2425
  8. Xiaorui Shi

    Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, United States
    For correspondence
    shix@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6068-1413

Funding

National Institute on Deafness and Other Communication Disorders (R01 DC015781)

  • Xiaorui Shi

National Institute on Deafness and Other Communication Disorders (R01-DC010844)

  • Xiaorui Shi

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

Ethics

Animal experimentation: All animal experiments reported were approved by the Oregon Health & Science University Institutional Animal Care and Use Committee (IACUC IP00000968).

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Yunpei Zhang
  2. Lingling Neng
  3. Kushal Sharma
  4. Zhiqiang Hou
  5. Anatasiya Johnson
  6. Junha Song
  7. Alain Dabdoub
  8. Xiaorui Shi
(2023)
Pericytes control vascular stability and auditory spiral ganglion neuron survival
eLife 12:e83486.
https://doi.org/10.7554/eLife.83486

Share this article

https://doi.org/10.7554/eLife.83486

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