GEO series

Suppression of endothelial ceramide de novo biosynthesis contributes to cardiometabolic diseases

GSE278555 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/01/24 Platform GPL24247

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: 4 × WT mice on chow diet (CD) vs 4 × WT mice on high fat diet (HFD) vs 4 × ECKO Nogo high fat diet (HFD)Groups 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: Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseasesNature communications · 2025

Summary (written by the submitters)

Metabolic disorders and obesity increase the risk for cardiovascular (CV) disease, including hypertension, atherosclerosis, and myocardial infarction. Systemic endothelial dysfunction, a well-established response to CV risk factors, precedes the development of CV diseases. However, growing evidence suggest that endothelial dysregulation also contributes to metabolic disorders, underlying a centric role of the endothelium in cardiometabolic diseases.

Read the full summary ↓

The accrual of the sphingolipid ceramide, bioactive molecule, has been causally implicated in endothelial dysfunction in vitro. However, direct in vivo evidence supporting the accrual of ceramide in the endothelium, underlying mechanisms, and pathological implications are lacking. Here, we showed that the suppression rather than the accrual of ceramides is causally linked to endothelial dysfunction, and imparts a pro-inflammatory and pro-atherosclerotic phenotype, contributing to both vascular and metabolic disorders. Mechanistically, the upregulation of Nogo-B and ORMDLs proteins, inhibitors of the first and rate limiting enzyme of the de novo biosynthesis, in the endothelium of obese and diabetic mice suppresses sphingolipid signaling, particularly ceramides and sphingosine-1-phosphate, resulting in vascular and metabolic dysfunctions. Systemic and endothelial specific deletion of Nogo-B restores sphingolipid signaling and functions of the endothelium, improves hypertension and lowers hepatic glucose production. Our results demonstrating that Nogo-B-mediated suppression of sphingolipid metabolism and signaling in the endothelium has pathological implication in cardiometabolic disorders and set a framework for the development of therapeutic strategies to treat these conditions.

Published in

Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases

Rubinelli L, Manzo OL, Sungho J et al. · Nature communications 2025 · PMID 40000621 · doi:10.1038/s41467-025-56869-9

This dataset

Open GSE278555 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 GSE278555_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 PRJNA1167768 and SRA study SRP536079. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40000621) ↗

Study design

4 × WT mice on chow diet (CD) vs 4 × WT mice on high fat diet (HFD) vs 4 × ECKO Nogo high fat diet (HFD)

Supports a between-group comparison across 12 samples.

How we read this: 3 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

GSM8548793 WT mice on chow diet (CD) replicate 1 WT mice on chow diet (C…
GSM8548794 WT mice on chow diet (CD) replicate 2 WT mice on chow diet (C…
GSM8548795 WT mice on chow diet (CD) replicate 3 WT mice on chow diet (C…
GSM8548796 WT mice on chow diet (CD) replicate 4 WT mice on chow diet (C…
GSM8548797 WT mice on high fat diet (HFD) replicate 1 WT mice on high fat die…
GSM8548798 WT mice on high fat diet (HFD) replicate 2 WT mice on high fat die…
GSM8548799 WT mice on high fat diet (HFD) replicate 3 WT mice on high fat die…
GSM8548800 WT mice on high fat diet (HFD) replicate 4 WT mice on high fat die…
GSM8548801 ECKO Nogo high fat diet (HFD) replicate 1 ECKO Nogo high fat diet…
GSM8548802 ECKO Nogo high fat diet (HFD) replicate 2 ECKO Nogo high fat diet…
GSM8548803 ECKO Nogo high fat diet (HFD) replicate 3 ECKO Nogo high fat diet…
GSM8548804 ECKO Nogo high fat diet (HFD) replicate 4 ECKO Nogo high fat diet…

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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.