GEO series

Stress dynamically modulates Neuronal Autophagy to gate depression onset

GSE287175 Mus musculus (mouse) RNA-seq (gene expression) 42 samples Submitted 2025/01/20 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 42 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: 42 samples: 14 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.
Paper: Stress dynamically modulates neuronal autophagy to gate depression onsetNature · 2025

Summary (written by the submitters)

Chronic stress remodels brain homeostasis, in which persistent change leads to depressive disorders. As a key modulator of brain homeostasis, it remains elusive whether and how brain autophagy is engaged in stress dynamics. Here, we discover that acute stress activates, whereas chronic stress suppresses, autophagy mainly in the lateral habenula (LHb).

Read the full summary ↓

Remarkably, systemic administration of distinct antidepressant drugs similarly restores autophagy function in the LHb, suggesting LHb autophagy as a common antidepressant target. Genetic ablation of LHb neuronal autophagy promotes stress susceptibility, whereas enhancing LHb autophagy exerts rapid antidepressant-like effects. LHb autophagy controls neuronal excitability, synaptic transmission and plasticity via on-demand degradation of glutamate receptors. Collectively, this study reveals a causal role of LHb autophagy in maintaining emotional homeostasis against stress. Disrupted LHb autophagy is implicated in the maladaptation to chronic stress, and its reversal by autophagy enhancers provides a novel antidepressant strategy.

Published in

Stress dynamically modulates neuronal autophagy to gate depression onset

Yang L, Guo C, Zheng Z et al. · Nature 2025 · PMID 40205038 · doi:10.1038/s41586-025-08807-4

This dataset

Open GSE287175 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 GSE287175_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 PRJNA1211554 and SRA study SRP557949. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40205038) ↗

Study design

14 conditions, mostly in triplicate

naïve mice with low FST scores, LHb, ×3 naïve mice with high FST scores, LHb, ×3 CRS mice with high FST scores, LHb, ×3 CRS mice with low FST scores, LHb, ×3 naïve mice, vHippo, ×3 CRS mice, vHippo, ×3 naïve mice, VTA, ×3 CRS mice, VTA, ×3 +6 more

Supports a between-group comparison across 42 samples.

How we read this: 14 replicated groups read from 42 sample titles; they account for 42 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

GSM8740506 naïve mice with low FST scores, LHb, rep1 naïve mice with low FST…
GSM8740507 naïve mice with low FST scores, LHb, rep2 naïve mice with low FST…
GSM8740508 naïve mice with low FST scores, LHb, rep3 naïve mice with low FST…
GSM8740509 naïve mice with high FST scores, LHb, rep1 naïve mice with high FS…
GSM8740510 naïve mice with high FST scores, LHb, rep2 naïve mice with high FS…
GSM8740511 naïve mice with high FST scores, LHb, rep3 naïve mice with high FS…
GSM8740512 CRS mice with high FST scores, LHb, rep1 CRS mice with high FST …
GSM8740513 CRS mice with high FST scores, LHb, rep2 CRS mice with high FST …
GSM8740514 CRS mice with high FST scores, LHb, rep3 CRS mice with high FST …
GSM8740515 CRS mice with low FST scores, LHb, rep1 CRS mice with low FST s…
GSM8740516 CRS mice with low FST scores, LHb, rep2 CRS mice with low FST s…
GSM8740517 CRS mice with low FST scores, LHb, rep3 CRS mice with low FST s…
GSM8740518 naïve mice, vHippo, rep1 naïve mice, vHippo,
GSM8740519 naïve mice, vHippo, rep2 naïve mice, vHippo,
GSM8740520 naïve mice, vHippo, rep3 naïve mice, vHippo,
GSM8740521 CRS mice, vHippo, rep1 CRS mice, vHippo,
GSM8740522 CRS mice, vHippo, rep2 CRS mice, vHippo,
GSM8740523 CRS mice, vHippo, rep3 CRS mice, vHippo,
GSM8740524 naïve mice, VTA, rep1 naïve mice, VTA,
GSM8740525 naïve mice, VTA, rep2 naïve mice, VTA,
GSM8740526 naïve mice, VTA, rep3 naïve mice, VTA,
GSM8740527 CRS mice, VTA, rep1 CRS mice, VTA,
GSM8740528 CRS mice, VTA, rep2 CRS mice, VTA,
GSM8740529 CRS mice, VTA, rep3 CRS mice, VTA,
GSM8740530 naïve mice, NAc, rep1 naïve mice, NAc,
GSM8740531 naïve mice, NAc, rep2 naïve mice, NAc,
GSM8740532 naïve mice, NAc, rep3 naïve mice, NAc,
GSM8740533 CRS mice, NAc, rep1 CRS mice, NAc,
GSM8740534 CRS mice, NAc, rep2 CRS mice, NAc,
GSM8740535 CRS mice, NAc, rep3 CRS mice, NAc,
GSM8740536 naïve mice, mPFC, rep1 naïve mice, mPFC,
GSM8740537 naïve mice, mPFC, rep2 naïve mice, mPFC,
GSM8740538 naïve mice, mPFC, rep3 naïve mice, mPFC,
GSM8740539 CRS mice, mPFC, rep1 CRS mice, mPFC,
GSM8740540 CRS mice, mPFC, rep2 CRS mice, mPFC,
GSM8740541 CRS mice, mPFC, rep3 CRS mice, mPFC,
GSM8740542 naïve mice, LH, rep1 naïve mice, LH,
GSM8740543 naïve mice, LH, rep2 naïve mice, LH,
GSM8740544 naïve mice, LH, rep3 naïve mice, LH,
GSM8740545 CRS mice, LH, rep1 CRS mice, LH,

+ 2 more — browse all 42 samples with per-sample file links →

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