Cochlear transcriptome analysis of an outbred mouse population (CFW)

Area of Science:

• Otolaryngology
• Genetics
• Cell Biology

Background:

• Age-related hearing loss (ARHL) is a prevalent condition in the elderly, but its genetic underpinnings and cellular mechanisms remain poorly understood.
• Identifying specific genes, cell types, and pathways is crucial for developing effective therapeutic interventions for ARHL.

Purpose of the Study:

• To comprehensively characterize the cell-type specific transcriptome of the aging mouse cochlea.
• To correlate cochlear cell type changes with auditory threshold variations in an outbred mouse model of ARHL.

Main Methods:

• Single-nucleus RNA sequencing (snRNA-seq) was employed on aging mouse cochleae.
• Cell types were identified through unsupervised clustering, marker gene analysis, and validated using Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH).
• Data was compared with existing datasets via the gEAR website.

Main Results:

• 60 unique cochlear cell types were identified, more than doubling previously defined types.
• Significant increases and decreases in specific cell subtypes, including hair cells, ganglion cells, and stria vascularis cells, were associated with reduced hearing acuity.
• This provides a detailed cellular atlas of the aging cochlea.

Conclusions:

• This study provides the first complete cell-type specific transcriptome of the aging mouse cochlea.
• Findings implicate specific cochlear cell subtypes in the mechanisms of age-related hearing loss.
• The identified cellular and molecular pathways offer potential targets for future therapeutic strategies.