Author:
Taukulis Ian A.,Olszewski Rafal T.,Korrapati Soumya,Fernandez Katharine A.,Boger Erich T.,Fitzgerald Tracy S.,Morell Robert J.,Cunningham Lisa L.,Hoa Michael
Abstract
The endocochlear potential (EP) generated by the stria vascularis (SV) is necessary for hair cell mechanotransduction in the mammalian cochlea. We sought to create a model of EP dysfunction for the purposes of transcriptional analysis and treatment testing. By administering a single dose of cisplatin, a commonly prescribed cancer treatment drug with ototoxic side effects, to the adult mouse, we acutely disrupt EP generation. By combining these data with single cell RNA-sequencing findings, we identify transcriptional changes induced by cisplatin exposure, and by extension transcriptional changes accompanying EP reduction, in the major cell types of the SV. We use these data to identify gene regulatory networks unique to cisplatin treated SV, as well as the differentially expressed and druggable gene targets within those networks. Our results reconstruct transcriptional responses that occur in gene expression on the cellular level while identifying possible targets for interventions not only in cisplatin ototoxicity but also in EP dysfunction.
Funder
National Institute on Deafness and Other Communication Disorders
Subject
Cellular and Molecular Neuroscience,Molecular Biology
Cited by
20 articles.
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