GEO series

Regulation of Redox Homeostasis by ATF4-MTHFD2 Axis during White Adipose Tissue Browning

GSE294416 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/05/13 Platform GPL28430

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 3 × Atf4WT iWAT, RT, biol vs 3 × Atf4AKO iWAT, RT, biol vs 3 × Atf4WT iWAT, cold, biol vs 3 × Atf4AKO iWAT, cold, biolGroups 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: Regulation of redox homeostasis by ATF4-MTHFD2 axis during white adipose tissue browningRedox biology · 2025

Summary (written by the submitters)

Maintaining redox balance is crucial for mitochondrial homeostasis. During browning of white adipocytes, both the quality and quantity of mitochondria undergo dramatic changes. However, the mechanisms controlling the redox balance in the mitochondria during this process remain unclear. In this study, we demonstrate that thermogenic activation occurs before mitochondrial biogenesis during cold-induced browning of inguinal white adipose tissue (iWAT) and is accompanied by increased mitochondrial stress and integrated stress response (ISR) signaling.

Read the full summary ↓

Specifically, cold exposure enhances the expression of ATF4, an ISR effector. Adipocyte-specific deletion of ATF4 results in increased energy expenditure, but paradoxically leads to a lower core body temperature, and heightened pro-inflammation in iWAT after cold exposure, which is restored by the antioxidant, MitoQ. Mechanistically, ATF4 regulates the redox balance through MTHFD2, an enzyme involved in mitochondrial redox homeostasis by NADPH generation. Cold exposure upregulates MTHFD2 expression in an ATF4-dependent manner, and its inhibition by DS18561882 in vivo leads to impaired cold- induced mitochondrial respiration similar to the effects of ATF4 loss. These findings suggest that ATF4 is essential for redox balance via MTHFD2, thereby affecting tissue homeostasis during iWAT browning.

Published in

Regulation of redox homeostasis by ATF4-MTHFD2 axis during white adipose tissue browning

Ginting RP, Pham-Bui HA, Munkhzul C et al. · Redox biology 2025 · PMID 40516456 · doi:10.1016/j.redox.2025.103715

This dataset

Open GSE294416 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 GSE294416_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 PRJNA1249416 and SRA study SRP577829. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40516456) ↗

Study design

3 × Atf4WT iWAT, RT, biol vs 3 × Atf4AKO iWAT, RT, biol vs 3 × Atf4WT iWAT, cold, biol vs 3 × Atf4AKO iWAT, cold, biol

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM8905103 Atf4WT iWAT, RT, biol rep 0 Atf4WT iWAT, RT, biol
GSM8905104 Atf4WT iWAT, RT, biol rep 1 Atf4WT iWAT, RT, biol
GSM8905105 Atf4WT iWAT, RT, biol rep 2 Atf4WT iWAT, RT, biol
GSM8905106 Atf4AKO iWAT, RT, biol rep 0 Atf4AKO iWAT, RT, biol
GSM8905107 Atf4AKO iWAT, RT, biol rep 1 Atf4AKO iWAT, RT, biol
GSM8905108 Atf4AKO iWAT, RT, biol rep 2 Atf4AKO iWAT, RT, biol
GSM8905109 Atf4WT iWAT, cold, biol rep 0 Atf4WT iWAT, cold, biol
GSM8905110 Atf4WT iWAT, cold, biol rep 1 Atf4WT iWAT, cold, biol
GSM8905111 Atf4WT iWAT, cold, biol rep 2 Atf4WT iWAT, cold, biol
GSM8905112 Atf4AKO iWAT, cold, biol rep 0 Atf4AKO iWAT, cold, biol
GSM8905113 Atf4AKO iWAT, cold, biol rep 1 Atf4AKO iWAT, cold, biol
GSM8905114 Atf4AKO iWAT, cold, biol rep 2 Atf4AKO iWAT, cold, biol

Datasets on a similar topic

GSE310044 Dietary sulfur amino acid restriction elicits a cold-like transcriptional response in inguinal but not epididymal white adipose tissue of male mice 110 samples shares adipose, white
GSE253735 Loss of skeletal muscle Bmal1 +/- Exercise Training [Mouse liver, heart, inguinal white adipose and lung tissues 64 samples shares adipose, white
GSE218943 Transcriptional profiling of mature murine adipocytes of the inguinal white adipose tissue depot following LPCAT3 deletion and dietary PUFA manipulation 30 samples shares adipose, white
GSE292928 Semaglutide and bariatric surgery induce distinct changes in the composition of mouse white adipose tissue 14 samples shares adipose, white
GSE254258 BBSome-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue (scRNA-Seq) 10 samples shares adipose, white
GSE281685 Transcription factor occupancy is affected by genetic variation in the white adipose tissue of C57BL6/j and 129S1/SvImJ mice [ChIP-seq] 16 samples shares adipose, white
GSE267727 Transcriptome profiling of non-islet metabolic tissues in ~500 DO mouse liver, adipose, heart, and skeletal muscle tissue from mice fed high-fat, high-sugar diet [heart] 482 samples shares adipose
GSE266549 Transcriptome profiling of non-islet metabolic tissues in ~500 DO mouse liver, adipose, and skeletal muscle tissue from mice fed high-fat, high-sugar diet. [Adipose] 468 samples shares adipose

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.