Pericytes control vascular stability and auditory spiral ganglion neuron survival
- Oregon Health & Science University, United States
- Lawrence Berkeley National Laboratory, United States
- 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.
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Author details
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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Pericytes control vascular stability and auditory spiral ganglion neuron survival
eLife 12:e83486.
https://doi.org/10.7554/eLife.83486
