GEO series

Reactivation of mTOR signaling slows neurodegeneration in a lysosomal storage disease

GSE275408 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/02/10 Platform GPL13112

At a glance

RNA-seq (gene expression) · mouse · 24 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: 24 samples: 6 × Brain, WT Control, vs 6 × Brain, TSC, vs 6 × Brain, HexbKO, vs 6 × Brain, KOTsc,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: Reactivation of mTOR signaling slows neurodegeneration in a lysosomal sphingolipid storage diseaseNeurobiology of disease · 2025

Summary (written by the submitters)

Sandhoff disease, a lysosomal storage disorder, is caused by pathogenic variants in the HEXB gene, resulting in the loss of β-hexosaminidase activity and accumulation of GM2 ganglioside and GA2 glycolipid. This accumulation occurs primarily in neurons, and leads to progressive neurodegeneration through a largely unknown process. Lysosomal storage diseases often exhibit dysfunctional mTOR signaling, a pathway crucial for proper neuronal development and function.

Read the full summary ↓

In this study, Sandhoff disease model mice exhibited reduced mTOR signaling in the brain. To test if restoring mTOR signaling could improve the disease phenotype, we genetically reduced expression of the mTOR inhibitor Tsc2 in these mice. Sandhoff disease mice with reactivated mTOR signaling displayed increased survival rates and motor function, especially in females, increased dendritic-spine density, and reduced neurodegeneration. Tsc2 reduction also partially rescued aberrant synaptic function–related gene expression. These findings imply that enhancing mTOR signaling could be a potential therapeutic strategy for lysosomal-based neurodegenerative diseases

Published in

Reactivation of mTOR signaling slows neurodegeneration in a lysosomal sphingolipid storage disease

Zhu H, Lee YT, Byrnes C et al. · Neurobiology of disease 2025 · PMID 39647513 · doi:10.1016/j.nbd.2024.106760

This dataset

Open GSE275408 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 GSE275408_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 PRJNA1150620 and SRA study SRP527923. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39647513) ↗

Study design

6 × Brain, WT Control, vs 6 × Brain, TSC, vs 6 × Brain, HexbKO, vs 6 × Brain, KOTsc,

Supports a between-group comparison across 24 samples.

How we read this: 4 replicated groups read from 24 sample titles; they account for 24 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

GSM8476412 Brain, WT Control, rep1 Brain, WT Control,
GSM8476413 Brain, WT Control, rep2 Brain, WT Control,
GSM8476414 Brain, WT Control, rep3 Brain, WT Control,
GSM8476415 Brain, WT Control, rep4 Brain, WT Control,
GSM8476416 Brain, WT Control, rep5 Brain, WT Control,
GSM8476417 Brain, WT Control, rep6 Brain, WT Control,
GSM8476418 Brain, TSC, rep1 Brain, TSC,
GSM8476419 Brain, TSC, rep2 Brain, TSC,
GSM8476420 Brain, TSC, rep3 Brain, TSC,
GSM8476421 Brain, TSC, rep4 Brain, TSC,
GSM8476422 Brain, TSC, rep5 Brain, TSC,
GSM8476423 Brain, TSC, rep6 Brain, TSC,
GSM8476424 Brain, HexbKO, rep1 Brain, HexbKO,
GSM8476425 Brain, HexbKO, rep2 Brain, HexbKO,
GSM8476426 Brain, HexbKO, rep3 Brain, HexbKO,
GSM8476427 Brain, HexbKO, rep4 Brain, HexbKO,
GSM8476428 Brain, HexbKO, rep5 Brain, HexbKO,
GSM8476429 Brain, HexbKO, rep6 Brain, HexbKO,
GSM8476430 Brain, KOTsc, rep1 Brain, KOTsc,
GSM8476431 Brain, KOTsc, rep2 Brain, KOTsc,
GSM8476432 Brain, KOTsc, rep3 Brain, KOTsc,
GSM8476433 Brain, KOTsc, rep4 Brain, KOTsc,
GSM8476434 Brain, KOTsc, rep5 Brain, KOTsc,
GSM8476435 Brain, KOTsc, rep6 Brain, KOTsc,

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