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.

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ObjectivesSingle‐cell RNA sequencing (scRNA‐Seq) is a new technique used to interrogate the transcriptome of individual cells within native tissues that have already resulted in key discoveries in auditory basic science research. Rapid advances in scRNA‐Seq make it likely that it will soon be translated into clinical medicine. The goal of this review is to inspire the use of scRNA‐Seq in otolaryngology by giving examples of how it can be applied to patient samples and how this information can be used clinically.MethodsStudies were selected based on the scientific quality and relevance to scRNA‐Seq. In addition to mouse auditory system (inner ear including hair cells and supporting cells, spiral ganglion neurons, and inner ear organoids), recent studies using human primary cell samples are discussed. We also perform our own analysis on publicly available, published scRNA‐Seq data from oral head and neck squamous cell carcinoma (HNSCC) samples to serve as an example of a clinically relevant application of scRNA‐Seq.ResultsStudies focusing on patient tissues show that scRNA‐Seq reveals tissue heterogeneity and rare‐cell types responsible for disease pathogenesis. The heterogeneity detected by scRNA‐Seq can result in both the identification of known or novel disease biomarkers and drug targets. Our analysis of HNSCC data gives an example for how otolaryngologists can use scRNA‐Seq for clinical use.ConclusionsAlthough there are limitations to the translation of scRNA‐Seq to the clinic, we show that its use in otolaryngology can give physicians insight into the tissue heterogeneity within their patient's diseased tissue giving them information on disease pathogenesis, novel disease biomarkers or druggable targets, and aid in selecting patient‐specific drug cocktails.