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Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder

GSE217568 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 32 samples Submitted 2025/07/09 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 32 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
32 samples: 6 conditions, mostly with about 5 replicates eachGroups 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
Major-depressive-disorder-associated dysregulation of ZBTB7A in orbitofrontal cortex promotes astrocyte-mediated stress susceptibilityNeuron · 2025
Summary (written by the submitters)
Overall risk for Major Depressive Disorder (MDD) is determined by complex interactions between genetic and environmental factors that influence epigenetic regulation of neuroplasticity and stress pathways. These mechanisms are specific to the distinct regulatory context within regionally-defined brain cell-types. Here, we employed genome-wide chromatin accessibility profiling of neuronal vs.
Read the full summary ↓
non-neuronal cells in orbitofrontal cortex (OFC) to capture regulatory signatures of MDD. We mapped genetic risk for MDD to active promoters of non-neuronal cell-types in OFC and identified MDD-specific open chromatin regions, which were differentially accessible exclusively in non-neuronal cells. Characterization of these loci revealed a key role for astrocyte dysfunction, and implicated the chromatin remodeling protein ZBTB7A, which coordinates wide-ranging cellular activation programs, including NF-kB inflammatory transcription. In mice, astrocyte-specific knockdown of Zbtb7a reversed chromatin remodeling, reactive astrocyte transcription, and behavioral deficits associated with chronic stress. Conversely, ZBTB7A overexpression in OFC astrocytes induced stress-related behavioral deficits, promoted widespread inflammatory gene expression, and drove pathophysiological OFC neuronal hyperactivity in response to a mild subthreshold stressor. Our data highlight a critical role for OFC astrocytes in the bidirectional regulation of stress vulnerability and pinpoint ZBTB7A as a key factor mediating maladaptive astrocyte plasticity and OFC neuronal hyperexcitability in MDD.
Published in
Major-depressive-disorder-associated dysregulation of ZBTB7A in orbitofrontal cortex promotes astrocyte-mediated stress susceptibility
Fulton SL, Bendl J, Di Salvo G et al. · Neuron 2025 · PMID 40516534 · doi:10.1016/j.neuron.2025.05.023
This dataset
Open GSE217568 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 GSE217568_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 PRJNA899552 and SRA study SRP406903. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40516534) ↗
Study design
6 conditions, mostly with about 5 replicates each
OFC astrocytes, OE_G ×6 OFC astrocytes, OE_Z ×6 OFC astrocytes, KD_GC ×5 OFC astrocytes, KD_GS ×5 OFC astrocytes, KD_ZC ×5 OFC astrocytes, KD_ZS ×5

Supports a between-group comparison across 32 samples.

How we read this: 6 replicated groups read from 32 sample titles; they account for 32 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
Datasets on a similar topic

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