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Heat-Shock Pathway Activation by TRC-051384 Protects Spiral Ganglion Neurons from Noise-Induced Hearing Loss [RNA-Seq]

GSE312476 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/12/11 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
12 samples: 3 × Cochlea, CBA/CaJ, 16W, mock vs 3 × Cochlea, CBA/CaJ, 16W, 100 dB SPL, 2h, vs 3 × Cochlea, CBA/CaJ, 16W, 100 dB SPL, 2h, 4h post, vs 3 × Cochlea, CBA/CaJ, 16W, 100 dB SPL, 2h, 8h post,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Heat-shock pathway activation by TRC051384 protects spiral ganglion neurons from noise-induced hearing lossbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Noise-induced hearing loss (NIHL) is a major public health problem caused by damage to cochlear hair cells, synapses, and spiral ganglion neurons (SGNs). However, effective treatments are completely lacking. We investigated cellular stress responses induced by loud noise in a mouse model of cochlear synaptopathy and tested whether selective activation of the dominant pathway identified could confer protection.
Read the full summary ↓
RNA sequencing and spatial transcriptomics revealed that noise exposure elicited a robust but transient upregulation of endoplasmic reticulum chaperones and proteasome subunits in SGNs and supporting cells. To target this response, we administered TRC051384, a small-molecule activator of the heat shock transcription factor Hsf1, prior to noise exposure. TRC051384 crossed the blood–labyrinth barrier and reached the cochlea, induced heat shock protein gene expression, and restored ubiquitin–proteasome function in SGNs. Notably, TRC051384 treatment improved auditory brainstem response recovery, preserved Wave I amplitudes, and maintained ribbon synapse density. These findings establish proteotoxic stress in SGNs as a central driver of NIHL and identify HSF1 activation as a promising therapeutic strategy.
Published in
Heat-shock pathway activation by TRC051384 protects spiral ganglion neurons from noise-induced hearing loss
Yu J, Ramirez MA, Wang YZ et al. · bioRxiv : the preprint server for biology 2025 · PMID 41415422 · doi:10.64898/2025.12.08.693048
This dataset
Open GSE312476 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE312476_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1373571 and SRA study SRP651324. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41415422) ↗
Study design
3 × Cochlea, CBA/CaJ, 16W, mock vs 3 × Cochlea, CBA/CaJ, 16W, 100 dB SPL, 2h, vs 3 × Cochlea, CBA/CaJ, 16W, 100 dB SPL, 2h, 4h post, vs 3 × Cochlea, CBA/CaJ, 16W, 100 dB SPL, 2h, 8h post,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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