Single cell and single nucleus RNA-Seq reveal cellular heterogeneity and homeostatic regulatory networks in adult mouse stria vascularis

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.

Single-cell sequencing: a powerful technique to understand the pathophysiology of auditory disorders

“…Single-cell RNA sequencing has led to the discovery of several genes in the SV implicated in hearing that were challenging to identify previously. These genes include Abcg1 and Heyl in marginal cells, P2rx2 and Kcnj16 in spindle cells, Nrp2 and Kcnj13 in intermediate cells, and Sox8 and Nr2f2 in basal cells (Korrapati et al, 2019). The information derived from the identification of genes implicated in sensorineural hearing loss (SNHL) using SCS can be used to develop cell-targeted therapeutic strategies.…”