Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets.

Autor:	Taukulis IA; Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Olszewski RT; Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Korrapati S; Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Fernandez KA; Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Boger ET; Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Fitzgerald TS; Mouse Auditory Testing Core Facility, National Institutes of Health, Bethesda, MD, United States., Morell RJ; Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Cunningham LL; Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States., Hoa M; Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2021 Sep 09; Vol. 14, pp. 718241. Date of Electronic Publication: 2021 Sep 09 (Print Publication: 2021).
DOI:	10.3389/fnmol.2021.718241
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Taukulis, Olszewski, Korrapati, Fernandez, Boger, Fitzgerald, Morell, Cunningham and Hoa.)
Databáze:	MEDLINE
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