Pericytes control vascular stability and auditory spiral ganglion neuron survival.
Yunpei ZhangLingling NengKushal SharmaZhiqiang HouAnatasiya JohnsonJunha SongAlain DabdoubXiaorui ShiPublished in: eLife (2023)
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 are not yet known. In this study, using an inducible and conditional pericyte depletion mouse (PDGFRB-CreER T2 ; 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.
Keyphrases
- vascular endothelial growth factor
- blood brain barrier
- endothelial cells
- mesenchymal stem cells
- stem cells
- healthcare
- public health
- single cell
- spinal cord
- cell therapy
- spinal cord injury
- risk assessment
- optic nerve
- climate change
- young adults
- optical coherence tomography
- health promotion
- childhood cancer
- angiotensin converting enzyme
- subarachnoid hemorrhage