Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection

This study aims to delineate the mechanisms through which intraperitoneal injection of gentamicin (GEN) influences the inner ear cells of mice by employing single-cell RNA sequencing (scRNA-seq) technology.

Eight-week-old Kunming mice were randomly assigned to three groups: a normal control group, a GEN group, and a GEN + dexamethasone (DEX) group. The mice received continuous intraperitoneal injections of the corresponding drugs for 10 days. Auditory brainstem response (ABR) was assessed to evaluate hearing threshold shifts, and cochlear tissues were harvested for scRNA-seq. The Seurat analysis workflow was employed for data quality control, dimensionality reduction clustering, and differential gene expression analysis.

ABR results demonstrated a significant elevation in hearing thresholds in the GEN group, whereas thresholds in the DEX group showed improvement but remained elevated compared to the NOR group (P < 0.05). Single-cell sequencing revealed notable alterations in the populations of outer hair cells, supporting cells, and immune cells in the GEN group. Analysis of differentially expressed genes identified significant downregulation of cell-specific genes Gbp6, Ppfia4 in hair cells of the GEN group, alongside upregulation of inflammation-related genes Nnat, Gh, indicating that hair cell damage and enhanced immune responses may be pivotal mechanisms underlying GEN-induced ototoxicity.

Utilizing scRNA-seq technology, this study uncovers substantial transcriptional changes induced by GEN in cochlear hair cells, supporting cells, and immune cells in mice, highlighting the role of inflammation and oxidative stress, TNF signaling pathways in its ototoxicity. DEX partially ameliorates hair cell damage.