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Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of Fragile X mice and identifies EPAC2 as a therapeutic target

GSE325852 Mus musculus (mouse) RNA-seq (gene expression) 69 samples Submitted 2026/03/30 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 69 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
69 samples: 16 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
Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of fragile X mice and identifies EPAC2 as a therapeutic targetNeuron · 2026
Summary (written by the submitters)
Symptoms of Fragile X Syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance. Here, we leverage cell type specific mRNA sequencing to profile molecular alterations of cortical excitatory (Camk2) and inhibitory (Pvalb) neurons in Fmr1 knockout (KO) mice, integrating transcriptomic results with circuit and behavioral readouts to prioritize novel therapeutic targets.
Read the full summary ↓
We uncovered significant genotype-by-cell interactions for differential gene expression in Camk2a and Pvalb translatomes, and, strikingly, the underlying signaling pathways were often altered in opposite directions. Among the 184 DEGs that were concordantly dysregulated across both cell types, only Rapgef4 (Epac2; upregulated in Fmr1 KO) was also an FMRP target, brain-enriched and associated with neurodevelopmental disorders. Treatment of Fmr1 KO mice with a specific EPAC2 antagonist restored cortical circuit function and ameliorated multiple behavioral phenotypes. Thus, EPAC2 should be considered as a potential target for therapy in FXS.
Published in
Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of fragile X mice and identifies EPAC2 as a therapeutic target
Suresh A, Kourdougli N, Nomura T et al. · Neuron 2026 · PMID 42155452 · doi:10.1016/j.neuron.2026.04.032
This dataset
Open GSE325852 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 GSE325852_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 PRJNA1442053 and SRA study SRP686246. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42155452) ↗
Study design
16 conditions, mostly with about 5 replicates each
RiboTag IP-Camk2(Excitatory) | WT | female | … ×6 RiboTag IP-PV (Parvalbumin) | WT | female | V… ×5 RiboTag IP-PV (Parvalbumin) | WT | male | V1 … ×5 RiboTag IP-PV (Parvalbumin) | KO | male | V1 … ×5 RiboTag IP-PV (Parvalbumin) | KO | female | V… ×5 RiboTag IP-PV (Parvalbumin) | WT | female | S… ×5 RiboTag IP-PV (Parvalbumin) | WT | male | S1 … ×5 RiboTag IP-PV (Parvalbumin) | KO | male | S1 … ×5 +9 more

Supports a between-group comparison across 68 samples.

How we read this: 16 replicated groups read from 69 sample titles; they account for 68 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

+ 29 more — browse all 69 samples with per-sample file links →

Datasets on a similar topic

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