Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets.
cisplatin
differential expression
endocochlear potential
gene regulatory networks
inner ear
scRNA-Seq
stria vascularis
Journal
Frontiers in molecular neuroscience
ISSN: 1662-5099
Titre abrégé: Front Mol Neurosci
Pays: Switzerland
ID NLM: 101477914
Informations de publication
Date de publication:
2021
2021
Historique:
received:
31
05
2021
accepted:
17
08
2021
entrez:
27
9
2021
pubmed:
28
9
2021
medline:
28
9
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34566577
doi: 10.3389/fnmol.2021.718241
pmc: PMC8458580
doi:
Types de publication
Journal Article
Langues
eng
Pagination
718241Informations de copyright
Copyright © 2021 Taukulis, Olszewski, Korrapati, Fernandez, Boger, Fitzgerald, Morell, Cunningham and Hoa.
Déclaration de conflit d'intérêts
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.
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