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PanethcellTNF-signalinginducesbacterialsepsis: transcriptome of intestinal epithelial cells 8h after TNF

GSE268933 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/06/05 Platform GPL19057
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 × IEC, TNF, vs 4 × IEC, Zinc+TNF, vs 2 × IEC, PBS, vs 2 × IEC, Zinc,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
Paneth cell TNF signaling induces gut bacterial translocation and sepsisCell host & microbe · 2024
Summary (written by the submitters)
Paneth Cells (PCs) are secretory cells located in the crypts of Lieberkühn of the small intestine. They produce antimicrobial peptides (AMPs) and are thought to keep the microbiome under control. The cytokine TNF, which functions mainly via its TNF receptor 1 (TNFR1 or P55), is a driving force in many inflammatory bowel disease (IBD) patients, but its impact on PCs is poorly known.
Read the full summary ↓
We have generated PC-specific P55 knockout mice (P55Paneth KO) and found that these mice are protected against lethal TNF-induced systemic inflammatory response syndrome (SIRS). The impact of TNF on PCs is characterized by morphological changes and by intestinal bacterial translocation into organs, such as liver, in which these bacteria induce expression of numerous genes, associated with typical sepsis signatures. The presence of these bacteria cause lethality of the mice. Based on bulk RNA-SEQ on pure PCs, P55 signaling stimulated mainly a type-I IFN response in the PCs, which drives the bacterial translocation and lethality via IFNAR1. Interestingly, based on ER stress reporter mice, PCs constitutively have high amounts of spliced XBP1 (XBP1s) protein, presumably to support their secretion of AMPs, and TNF eradicates this XBP1s production, leading to failure of the unfolded protein response (UPR). This causes reduced antimicrobial activity in PCs, in a P55 and IFNAR1-dependent way. Our data suggest a novel axis induced by TNF in PCs, leading to interferon-induced UPR failure causing lethal bacterial translocation to the liver (and other organs)
Published in
Paneth cell TNF signaling induces gut bacterial translocation and sepsis
Wallaeys C, Garcia-Gonzalez N, Timmermans S et al. · Cell host & microbe 2024 · PMID 39243761 · doi:10.1016/j.chom.2024.08.007
This dataset
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.

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 GSE268933_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1119480 and SRA study SRP511496. Searching any of these in the dataset finder brings you back here.

Study design
4 × IEC, TNF, vs 4 × IEC, Zinc+TNF, vs 2 × IEC, PBS, vs 2 × IEC, Zinc,

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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