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.

中文翻译：

---

顺铂治疗的成人血管纹的单细胞 RNA 测序鉴定了细胞类型特异性调控网络和新的治疗基因靶点。

血管纹 (SV) 产生的耳蜗内电位 (EP) 对于哺乳动物耳蜗中的毛细胞机械转导是必需的。我们试图创建 EP 功能障碍模型，用于转录分析和治疗测试。通过对成年小鼠施用单剂量的顺铂（一种具有耳毒性副作用的常用癌症治疗药物），我们可以严重破坏 EP 的产生。通过将这些数据与单细胞 RNA 测序结果相结合，我们确定了 SV 主要细胞类型中由顺铂暴露引起的转录变化，以及伴随 EP 减少而延伸的转录变化。我们利用这些数据来识别顺铂治疗的 SV 特有的基因调控网络，以及这些网络中差异表达和可药物化的基因靶点。我们的结果重建了细胞水平上基因表达中发生的转录反应，同时确定了干预顺铂耳毒性和 EP 功能障碍的可能目标。