GEO series

Multiomic single nuclei profiling of a mouse model of Alzheimer’s disease reveals that ACSS2 confers neuronal resilience to tauopathy [ChIP-seq]

GSE294751 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 20 samples Submitted 2026/06/18 Platform GPL19057

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 20 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Mus musculus (mouse)
Samples: 20 samples: 8 conditions, mostly in triplicateGroups 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.

Summary (written by the submitters)

Loss of cell identity and global epigenomic dysregulation are emerging as key contributors to Alzheimer’s disease (AD). The mechanisms by which protective or risk-conferring epigenetic marks are established and maintained are under intense investigation. ACSS2 (Acetyl-CoA Synthetase 2) is a key metabolic enzyme that is nuclear-localized in neurons.

Read the full summary ↓

In healthy brains, ACSS2 fuels histone acetylation and drives expression of neuronal genes that regulate learning and memory. Here, we examine how loss of ACSS2 contributes to AD-associated cellular, genomic and behavioral outcomes, focusing on long-term steady state changes. Using a mouse model of human pathological AD-Tau injection, we show that loss of ACSS2 exacerbates Tau-related memory impairments, while dietary supplementation of acetate rescues learning in an ACSS2-dependent manner. Combining state-of-the-art proteomic and genomic approaches, we demonstrate that this effect is accompanied by ACSS2-dependent incorporation of acetate into hippocampal histone acetylation, which facilitates gene expression programs related to learning. We identify the most severely affected hippocampal neuronal populations, including pyramidal cells of the perforant pathway and Cajal-Retzius cells. Overall, these results reveal ACSS2 as a neuroprotective metabolic enzyme in key hippocampal neuronal populations, and dysregulation of which may play an important role in the etiology of AD. These findings may guide development of future therapies for AD, other tauopathies and related dementia.

This dataset

Open GSE294751 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE294751_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1251553 and SRA study SRP579011. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

8 conditions, mostly in triplicate

Input.Tau-KO ×3 Input.Tau-WT ×3 H3K27ac.Tau-KO ×3 H3K27ac.Tau-WT ×3 Input.PBS-KO ×2 Input.PBS-WT ×2 H3K27ac.PBS-KO ×2 H3K27ac.PBS-WT ×2

Supports a between-group comparison across 20 samples.

How we read this: 8 replicated groups read from 20 sample titles; they account for 20 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

GSM8918999 Input.Tau-KO.321 Input.Tau-KO
GSM8919000 Input.Tau-KO.322 Input.Tau-KO
GSM8919001 Input.Tau-KO.323 Input.Tau-KO
GSM8919002 Input.Tau-WT.333 Input.Tau-WT
GSM8919003 Input.Tau-WT.334 Input.Tau-WT
GSM8919004 Input.Tau-WT.335 Input.Tau-WT
GSM8919005 Input.PBS-KO.353 Input.PBS-KO
GSM8919006 Input.PBS-KO.354 Input.PBS-KO
GSM8919007 Input.PBS-WT.362 Input.PBS-WT
GSM8919008 Input.PBS-WT.363 Input.PBS-WT
GSM8919009 H3K27ac.Tau-KO.321 H3K27ac.Tau-KO
GSM8919010 H3K27ac.Tau-KO.322 H3K27ac.Tau-KO
GSM8919011 H3K27ac.Tau-KO.323 H3K27ac.Tau-KO
GSM8919012 H3K27ac.Tau-WT.333 H3K27ac.Tau-WT
GSM8919013 H3K27ac.Tau-WT.334 H3K27ac.Tau-WT
GSM8919014 H3K27ac.Tau-WT.335 H3K27ac.Tau-WT
GSM8919015 H3K27ac.PBS-KO.353 H3K27ac.PBS-KO
GSM8919016 H3K27ac.PBS-KO.354 H3K27ac.PBS-KO
GSM8919017 H3K27ac.PBS-WT.362 H3K27ac.PBS-WT
GSM8919018 H3K27ac.PBS-WT.363 H3K27ac.PBS-WT

Datasets on a similar topic

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GSE292137 Excitatory Neuronal ErbB4 Drives Early Pathophysiology of Alzheimer's Disease 18 samples shares alzheimer, neuronal
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