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An ER-anchored peptide C4orf3/ALN controls UCP1-independent Ca2+ cycling thermogenesis in adipose tissue

GSE268770 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/03/28 Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 6 × iWAT-ALNKO vs 6 × iWAT-DKO vs 6 × iWAT-UCP1KO vs 6 × iWAT-wtGroups 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
Identification of a molecular resistor that controls UCP1-independent Ca(2+) cycling thermogenesis in adipose tissueCell metabolism · 2025
Summary (written by the submitters)
Adipose tissue thermogenesis contributes to energy balance via mitochondrial uncoupling protein 1 (UCP1) and UCP1-independent pathways. Among UCP1-independent thermogenic mechanisms, one involves Ca2+ cycling via SERCA2b in subcutaneous adipose tissues; however, the molecular underpinnings of this process remain elusive. Here, we report that an ER-membrane anchored peptide C4orf3 (also known as anotherregulin, ALN) uncouples its Ca2+ transport from ATP-hydrolysis by interacting via the cytoplasmic domain, rendering the SERCA2b-C4orf3/ALN complex exothermic.
Read the full summary ↓
Loss of C4orf3/ALN improved the energetic efficiency of SERCA2-dependent Ca2+ transport, thereby reducing adipose tissue thermogenesis and increasing the adiposity of mice. In turn, overexpression of C4orf3/ALN promotes Ca2+ cycling thermogenesis in the microsomal compartment. Of note, genetic depletion of C4orf3 led to compensatory activation of mitochondrial thermogenesis via UCP1 following cold challenge. We found that genetic loss of both C4orf3 and Ucp1 additively impaired cold tolerance in vivo. Together, this study uncovers the molecular mechanisms and the physiological role of UCP1-independent Ca2+ cycling thermogenesis in adipose tissue. This RNA-seq data set showed that double knockdown (DKO) of UCP1 and C4orf3/ALN increased lipid catabolism in adipose tissue.
Published in
Identification of a molecular resistor that controls UCP1-independent Ca(2+) cycling thermogenesis in adipose tissue
Auger C, Li M, Fujimoto M et al. · Cell metabolism 2025 · PMID 40199326 · doi:10.1016/j.cmet.2025.03.009
This dataset
Open GSE268770 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 GSE268770_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 PRJNA1118717 and SRA study SRP511031. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40199326) ↗
Study design
6 × iWAT-ALNKO vs 6 × iWAT-DKO vs 6 × iWAT-UCP1KO vs 6 × iWAT-wt

Supports a between-group comparison across 24 samples.

How we read this: 4 replicated groups read from 24 sample titles; they account for 24 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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