← BioTransfer GEO Dataset Finder
GEO series

ACSS2 upregulation enhances neuronal resilience to aging and neurodegeneration [RNA-seq]

GSE254996 Mus musculus (mouse) RNA-seq (gene expression) 98 samples Submitted 2025/12/09 Platform GPL21626Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 98 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
98 samples: 98 samples, each with a distinct title — no replicated groupsGroups 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
ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegenerationProceedings of the National Academy of Sciences of the United States of America · 2026
Summary (written by the submitters)
Epigenetic mechanisms, including histone acetylation, play a key role in learning and memory, with recent evidence of a role in neuronal function in Alzheimer?s disease and Related Dementia (ADRD). Acetyl-CoA synthetase 2 (ACSS2), an enzyme that generates acetyl-CoA, is central to histone acetylation and gene regulation, particularly in neurons, due to their unique metabolic demands and their postmitotic state.
Read the full summary ↓
ACSS2 can be recruited to the nucleus and to chromatin, locally supplying acetyl-CoA to directly fuel histone acetyltransferase enzymes and key neuronal gene expression. This regulatory mechanism may be a promising target for therapeutic intervention in neurodegenerative diseases because systemic ACSS2 deletion in mice, although largely normal in physiology, is greatly impaired in memory. Here we investigated whether increasing levels of ACSS2 could protect neurons against disease and age-associated cognitive decline. Given the role of tau in ADRD, we used primary hippocampal neurons that mimic the sporadic development of tau pathology, and used the P301S transgenic mouse model for tau-induced memory decline. Our results show in these in vitro and in vivo models of tauopathy, that ACSS2 upregulation mitigates tau-induced transcriptional alterations, enhances neuronal resilience against tau pathology, improves long-term potentiation, and ameliorates memory deficits. Expanding upon these findings, we investigated deficits in aged mice, and reveal that increasing histone acetylation through ACSS2 upregulation improves age-associated memory decline. These findings indicate that increasing ACSS2 is highly effective in countering age- and tau-induced transcriptome changes, preserving elevated levels of synaptic genes, and safeguarding synaptic integrity. We thus highlight ACSS2 as a key player in the epigenetic regulation of cognitive aging and ADRD, providing a foundation for targeted therapeutics to enhance brain resilience and function.
Published in
ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration
Pourshafie N, Alexander DC, Xu H et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 41512015 · doi:10.1073/pnas.2503834122
This dataset
Open GSE254996 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 GSE254996_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 PRJNA1072996 and SRA study SRP487936. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41512015) ↗
Study design
98 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 6 samples read as cases, 12 as controls.

How we read this: Read from 98 sample titles: 98 distinct titles with little repetition. 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

+ 58 more — browse all 98 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.