Abstract
The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.
Highlights
Ionic homeostasis in the endolymph-containing compartment of the cochlea, the scala media, is a critical factor in enabling proper hair cell mechanotransduction and hearing (Wangemann, 2002, 2006; Hibino et al, 2010)
We define the implications of these data for: (1) using and developing mouse models to define the contribution of each Stria Vascularis (SV) cell type to SV function and hearing at the level of gene expression, (2) understanding ion homeostatic mechanisms broadly in the inner ear, (3) contributing to efforts to develop targeted SV gene therapy through the use of cell type-specific promoters, (4) identifying druggable gene targets and the potential for repurposing existing pharmacotherapies to treat inner ear disease, and (5) use of these data to identify cell type-specific contributions to disease
In characterizing adult SV cellular heterogeneity using transcriptional profiling, these data provide opportunities to study adult SV cell type-specific mechanisms that contribute to endocochlear potential (EP) generation and whose dysfunction results in hearing loss
Summary
Ionic homeostasis in the endolymph-containing compartment of the cochlea, the scala media, is a critical factor in enabling proper hair cell mechanotransduction and hearing (Wangemann, 2002, 2006; Hibino et al, 2010). The endolymph is the atypical potassium rich extracellular fluid of the cochlear duct. This high potassium concentration results in a +80 millivolt (mV) positive potential known as the endocochlear potential (EP) (Wangemann, 2002; Patuzzi, 2011). The stria vascularis (SV), a non- sensory epithelial tissue in the lateral wall of the cochlea, generates and maintains this high potassium concentration and the EP. The SV is a complex, heterogenous tissue consisting of several cell types that work together to generate and maintain the EP. Cell types identified as critical to this role far include
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