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The spatiotemporal expression profile of ATF3 determines the fate of smooth muscle cells in abdominal aortic aneurysm development

GSE261595 Mus musculus (mouse) RNA-seq (gene expression) 10 samples Submitted 2024/09/01 Platform GPL30215
At a glance

RNA-seq (gene expression) · mouse · 10 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
10 samples: 4 × Muscle,Ang II-induced AAA, vs 3 × Muscle,sham control, vs 3 × Muscle,Ang II-induced lesion,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.
Summary (written by the submitters)
Background: Abdominal Aortic Aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. Activating transcription factor (ATF) 3 has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive.
Read the full summary ↓
Methods: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell (VSMC)-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 (rAAV9) vectors carrying ATF3, or shRNA-ATF3 with SM22α promoter were used in AngII (angiotensin II) induced AAA mice. In human and murine VSMCs, gain or loss of function experiments were performed to investigate the role of ATF3 in VSMC proliferation and apoptosis. Results: In both AngII-induced AAA mice and AAA patients, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in VSMC promoted AAA formation in AngII-induced AAA mice. PDGFRB was identified as the target of ATF3, which mediated VSMC proliferation in response to TNF-alpha at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our ChIP results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (Andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. Conclusions: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.
This dataset
Open GSE261595 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 GSE261595_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 PRJNA1088060 and SRA study SRP495253. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
4 × Muscle,Ang II-induced AAA, vs 3 × Muscle,sham control, vs 3 × Muscle,Ang II-induced lesion,

Supports a case/control comparison: 7 samples read as cases, 3 as controls.

How we read this: 3 replicated groups read from 10 sample titles; they account for 10 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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