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Neutrophil KLF2 regulates inflammasome-dependent neonatal mortality from endotoxemia

GSE278604 Mus musculus (mouse) RNA-seq (gene expression) 28 samples Submitted 2025/03/10 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 28 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
28 samples: 7 × P4Cre vs 7 × P4KO vs 7 × P12Cre vs 7 × P12KOGroups 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)
Preterm neonates die at a significantly higher rate from sepsis than full-term neonates, attributable to their dysregulated immune response. In addition to tissue destruction caused directly by bacterial invasion, an overwhelming cytokine response by the immune cells to bacterial antigens also results in collateral damage. Sepsis leads to decreased gene expression of a critical transcription factor, Kruppel-like factor-2 (KLF2), a tonic repressor of myeloid cell activation.
Read the full summary ↓
KLF2 gene expression is also lower in murine pups at an earlier postnatal age. Using a murine model of myeloid-KLF2 deletion, we show that loss of KLF2 leads to decreased survival after endotoxemia in a developmentally dependent manner, with increased mortality at postnatal day 4 (P4) compared to P12 pups. This survival is significantly increased by neutrophil depletion before endotoxemia. P4 knockout pups have increased pro-inflammatory cytokine levels after endotoxemia compared to P4 controls or P12 pups, with significantly increased levels of IL-1b, an end product of the activation of the NLRP3 inflammasome complex. Both loss of myeloid KLF2 and a younger postnatal age lead to increased NLRP3 protein expression and release of IL-1b in bone marrow neutrophils. Inhibition of NLRP3 inflammasome activation by MCC950 significantly increased survival after endotoxemia in P4 pups. Transcriptomic analysis of bone marrow neutrophils showed that loss of myeloid-KLF2 is associated with gene enrichment of pro-inflammatory pathways in a developmentally dependent manner. These data suggest that targeting KLF2 could be a novel strategy to decrease the pro-inflammatory cytokine storm in neonatal sepsis and improve survival in neonates with sepsis.
This dataset
Open GSE278604 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 GSE278604_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 PRJNA1168073 and SRA study SRP536605. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
7 × P4Cre vs 7 × P4KO vs 7 × P12Cre vs 7 × P12KO

Supports a between-group comparison across 28 samples.

How we read this: 4 replicated groups read from 28 sample titles; they account for 28 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
Datasets on a similar topic

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