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Effect of conditional SMC specific deletion of ADAR1 with constitutive deletion of RNA sensor MDA5 on mouse aortic single cell transcriptomic profile and effect on atherosclerosis

GSE280641 Mus musculus (mouse) Single-cell RNA-seq 12 samples Submitted 2025/07/29 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 12 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
12 samples: 3 × ADAR_MDA5_nTdt vs 3 × ADAR_MDA5_Tdt vs 3 × ADARhet_MDA5het_Tdt vs 3 × ADARhet_MDA5het_nTdtGroups 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
Smooth muscle expression of RNA editing enzyme ADAR1 controls activation of the RNA sensor MDA5 in atherosclerosisNature cardiovascular research · 2025
Summary (written by the submitters)
Mapping the genomic architecture of complex disease has been predicated on the understanding that genetic variants influence disease risk through modifying gene expression. However, recent discoveries have revealed that a significant burden of disease heritability in common autoinflammatory disorders and coronary artery disease is mediated through genetic variation modifying post-transcriptional modification of RNA through adenosine-to-inosine (A-to-I) RNA editing.
Read the full summary ↓
This common RNA modification is catalyzed by ADAR enzymes, where ADAR1 edits specific immunogenic double stranded RNA (dsRNA) to prevent activation of the double strand RNA (dsRNA) sensor MDA5 (IFIH1) and stimulation of an interferon stimulated gene (ISG) response. Multiple lines of human genetic data indicate impaired RNA editing and increased dsRNA sensing by MDA5 to be an important mechanism of coronary artery disease (CAD) risk. Here, we provide a crucial link between observations in human genetics and mechanistic cell biology leading to progression of CAD. Through analysis of human atherosclerotic plaque, we implicate the vascular smooth muscle cell (SMC) to have a unique requirement for RNA editing, and that ISG induction occurs in SMC phenotypic modulation, implicating MDA5 activation. Through culture of human coronary artery SMCs, generation of a conditional SMC specific Adar1 deletion mouse model on a pro-atherosclerosis background with additional constitutive deletion of MDA5 (Ifih1), and with incorporation of single cell RNA sequencing cellular profiling, we further show that Adar1 controls SMC phenotypic state by regulating Mda5 activation, is required to maintain vascular integrity, and controls progression of atherosclerosis and vascular calcification. Through this work, we describe a fundamental mechanism of CAD, where cell type and context specific RNA editing and sensing of dsRNA mediates disease progression, bridging our understanding of human genetics and disease causality.
Published in
Smooth muscle expression of RNA editing enzyme ADAR1 controls activation of the RNA sensor MDA5 in atherosclerosis
Weldy CS, Li Q, Monteiro JP et al. · Nature cardiovascular research 2025 · PMID 40958051 · doi:10.1038/s44161-025-00710-5
This dataset
Open GSE280641 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 GSE280641_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1179865 and SRA study SRP541988. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40958051) ↗
Study design
3 × ADAR_MDA5_nTdt vs 3 × ADAR_MDA5_Tdt vs 3 × ADARhet_MDA5het_Tdt vs 3 × ADARhet_MDA5het_nTdt

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
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