GEO series

CPEB2-activated Prdm16 translation promotes brown adipocyte function and prevents obesity

GSE242882 Mus musculus (mouse) RNA-seq (gene expression) 22 samples Submitted 2024/09/24 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 22 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: 22 samples: 6 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: CPEB2-activated Prdm16 translation promotes brown adipocyte function and prevents obesityMolecular metabolism · 2024

Summary (written by the submitters)

Objective Brown adipose tissue (BAT) plays an important role in mammalian thermogenesis through the expression of uncoupling protein 1 (UCP1). Our previous study identified cytoplasmic polyadenylation element binding protein 2 (CPEB2) as a key regulator that activates the translation of Ucp1 with a long 3′-untranslated region (Ucp1L) in response to adrenergic signaling.

Read the full summary ↓

Mice lacking CPEB2 or Ucp1L exhibited reduced UCP1 expression and impaired thermogenesis; however, only CPEB2-null mice displayed obesogenic phenotypes. Hence, this study aims to investigate how CPEB2-controlled translation impacts body weight. Methods Body weight measurements were conducted on mice with global knockout (KO) of CPEB2, UCP1 or Ucp1L, as well as those with conditional knockout of CPEB2 in neurons or adipose tissues. RNA sequencing coupled with bioinformatics analysis was used to identify dysregulated gene expression in CPEB2-deficient BAT. The role of CPEB2 in regulating PRD1-BF1-RIZ1 homologous-domain containing 16 (PRDM16) expression was subsequently confirmed by RT-qPCR, Western blotting, polysomal profiling and luciferase reporter assays. Adeno-associated viruses (AAV) expressing CPEB2 or PRDM16 were delivered into BAT to assess their efficacy in mitigating weight gain in CPEB2-KO mice. Results We validated that defective BAT function contributed to the increased weight gain in CPEB2-KO mice. Transcriptomic profiling revealed upregulated expression of genes associated with muscle development in CPEB2-KO BAT. Given that both brown adipocytes and myocytes stem from myogenic factor 5-expressing precursors, with their cell-fate differentiation regulated by PRDM16, we identified that Prdm16 was translationally upregulated by CPEB2. Ectopic expression of PRDM16 in CPEB2-deprived BAT restored gene expression profiles and decreased weight gain in CPEB2-KO mice. Conclusions In addition to Ucp1L, activation of Prdm16 translation by CPEB2 is critical for sustaining brown adipocyte function. These findings unveil a new layer of post-transcriptional regulation governed by CPEB2, fine-tuning thermogenic and metabolic activities of brown adipocytes to control body weight.

Published in

CPEB2-activated Prdm16 translation promotes brown adipocyte function and prevents obesity

Lu WH, Chen HF, King PC et al. · Molecular metabolism 2024 · PMID 39305947 · doi:10.1016/j.molmet.2024.102034

This dataset

Open GSE242882 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 GSE242882_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 PRJNA1015224 and SRA study SRP459740. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39305947) ↗

Study design

6 conditions, mostly in triplicate

BAT, CP2-WT, ×5 BAT, CP2-KO, ×5 BAT, CP2-WT +GFP, ×3 BAT, CP2-WT +PRDM16, ×3 BAT, CP2-KO +GFP, ×3 BAT, CP2-KO +PRDM16, ×3

Supports a between-group comparison across 22 samples.

How we read this: 6 replicated groups read from 22 sample titles; they account for 22 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

GSM7774318 BAT, CP2-WT, rep1 BAT, CP2-WT,
GSM7774319 BAT, CP2-WT, rep2 BAT, CP2-WT,
GSM7774320 BAT, CP2-WT, rep3 BAT, CP2-WT,
GSM7774321 BAT, CP2-WT, rep4 BAT, CP2-WT,
GSM7774322 BAT, CP2-WT, rep5 BAT, CP2-WT,
GSM7774323 BAT, CP2-KO, rep1 BAT, CP2-KO,
GSM7774324 BAT, CP2-KO, rep2 BAT, CP2-KO,
GSM7774325 BAT, CP2-KO, rep3 BAT, CP2-KO,
GSM7774326 BAT, CP2-KO, rep4 BAT, CP2-KO,
GSM7774327 BAT, CP2-KO, rep5 BAT, CP2-KO,
GSM7774328 BAT, CP2-WT +GFP, rep1 BAT, CP2-WT +GFP,
GSM7774329 BAT, CP2-WT +GFP, rep2 BAT, CP2-WT +GFP,
GSM7774330 BAT, CP2-WT +GFP, rep3 BAT, CP2-WT +GFP,
GSM7774331 BAT, CP2-WT +PRDM16, rep1 BAT, CP2-WT +PRDM16,
GSM7774332 BAT, CP2-WT +PRDM16, rep2 BAT, CP2-WT +PRDM16,
GSM7774333 BAT, CP2-WT +PRDM16, rep3 BAT, CP2-WT +PRDM16,
GSM7774334 BAT, CP2-KO +GFP, rep1 BAT, CP2-KO +GFP,
GSM7774335 BAT, CP2-KO +GFP, rep2 BAT, CP2-KO +GFP,
GSM7774336 BAT, CP2-KO +GFP, rep3 BAT, CP2-KO +GFP,
GSM7774337 BAT, CP2-KO +PRDM16, rep1 BAT, CP2-KO +PRDM16,
GSM7774338 BAT, CP2-KO +PRDM16, rep2 BAT, CP2-KO +PRDM16,
GSM7774339 BAT, CP2-KO +PRDM16, rep3 BAT, CP2-KO +PRDM16,

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