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Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repair

GSE262847 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/04/07 Platform GPL24247
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: 7 conditions, mostly with about 4 replicates eachGroups 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
Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repairNature · 2024
Summary (written by the submitters)
Pyroptosis is a lytic cell death mode that helps limit the spread of infections and is also linked to pathology in sterile inflammatory diseases and autoimmune diseases. During pyroptosis, inflammasome activation and the engagement of caspase-1 lead to cell death, along with the maturation and secretion of the inflammatory cytokine interleukin 1β (IL-1β).
Read the full summary ↓
The dominant effect of IL-1β in promoting tissue inflammation has clouded the potential influence of other factors released from pyroptotic cells. Here, using a system where macrophages are induced to undergo pyroptosis without IL-1β/⍺ release (denoted Pyro-1), we uncover unexpected beneficial effects of the Pyro-1 secretome. First, we noted that the Pyro-1 supernatants upregulated gene signatures linked to migration, cellular proliferation, and wound healing. Consistent with this gene signature, Pyro-1 supernatants boosted migration of primary fibroblasts and macrophages, as well as faster wound closure in vitro, and improved tissue repair in vivo. In mechanistic studies, lipidomics and metabolomics of the Pyro-1 supernatants identified the presence of both oxylipins and metabolites, linking them to pro-wound healing effects. Focusing specifically on the oxylipin prostaglandin E2 (PGE2), we find that PGE2 synthesis is induced de novo during pyroptosis, downstream of caspase-1 activation, and COX2 activity; further, PGE2 synthesis occurs late in pyroptosis, with its release dependent on Gasdermin D pores opened during pyroptosis. As for the pyroptotic metabolites, they link to immune cell infiltration into the wounds, and polarization to CD301+ macrophages. Collectively, these data advance the concept that the pyroptotic secretome 1 Mehrotra et al., Page No. possesses oxylipins and metabolites with tissue repair properties that may be harnessed therapeutically.
Published in
Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repair
Mehrotra P, Maschalidi S, Boeckaerts L et al. · Nature 2024 · PMID 38926576 · doi:10.1038/s41586-024-07585-9
This dataset
Open GSE262847 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 GSE262847_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 PRJNA1093474 and SRA study SRP498740. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38926576) ↗
Study design
7 conditions, mostly with about 4 replicates each
BMDMs, treated with supernatants from alive (… ×4 BMDMs, treated with supernatants from apoptot… ×4 BMDMs, treated with supernatants from alive (… ×4 BMDMs, treated with supernatants from alive (… ×4 BMDMs, treated with supernatant from alive (+… ×4 BMDMs, treated with supernatants from pyropto… ×2 BMDMs, treated with supernatants from pyropto… ×2

Supports a between-group comparison across 24 samples.

How we read this: 7 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
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