Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets
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 cisplati...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.718241/full |
| _version_ | 1819110226194857984 |
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| author | Ian A. Taukulis Rafal T. Olszewski Soumya Korrapati Katharine A. Fernandez Erich T. Boger Tracy S. Fitzgerald Robert J. Morell Lisa L. Cunningham Michael Hoa |
| author_facet | Ian A. Taukulis Rafal T. Olszewski Soumya Korrapati Katharine A. Fernandez Erich T. Boger Tracy S. Fitzgerald Robert J. Morell Lisa L. Cunningham Michael Hoa |
| author_sort | Ian A. Taukulis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T03:38:21Z |
| format | Article |
| id | doaj.art-2dc1b5979a9047d7a04294e21a85153f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T03:38:21Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-2dc1b5979a9047d7a04294e21a85153f2022-12-21T18:40:19ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-09-011410.3389/fnmol.2021.718241718241Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene TargetsIan A. Taukulis0Rafal T. Olszewski1Soumya Korrapati2Katharine A. Fernandez3Erich T. Boger4Tracy S. Fitzgerald5Robert J. Morell6Lisa L. Cunningham7Michael Hoa8Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesAuditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesAuditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesLaboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesGenomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesMouse Auditory Testing Core Facility, National Institutes of Health, Bethesda, MD, United StatesGenomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesLaboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesAuditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fnmol.2021.718241/fullstria vascularisendocochlear potentialinner earscRNA-Seqcisplatindifferential expression |
| spellingShingle | Ian A. Taukulis Rafal T. Olszewski Soumya Korrapati Katharine A. Fernandez Erich T. Boger Tracy S. Fitzgerald Robert J. Morell Lisa L. Cunningham Michael Hoa Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets Frontiers in Molecular Neuroscience stria vascularis endocochlear potential inner ear scRNA-Seq cisplatin differential expression |
| title | Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets |
| title_full | Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets |
| title_fullStr | Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets |
| title_full_unstemmed | Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets |
| title_short | Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets |
| title_sort | single cell rna seq of cisplatin treated adult stria vascularis identifies cell type specific regulatory networks and novel therapeutic gene targets |
| topic | stria vascularis endocochlear potential inner ear scRNA-Seq cisplatin differential expression |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.718241/full |
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