GEO series

A critical role for Hepatocyte Nuclear Factor 4 alpha in polymicrobial sepsis-associated metabolic reprogramming and death: effect of CLP/SHAM in Hnf4a WT and KO mice

GSE260635 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/03/12 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples: 4 × liver, KO CLP, vs 4 × liver, KO SHAM, vs 4 × liver, WT CLP, vs 4 × liver, WT SHAM,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: A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and deathEMBO molecular medicine · 2024

Summary (written by the submitters)

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has strong impact on the expression of several important nuclear receptors, including PPARα.

Read the full summary ↓

HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis and organ damage and prevents an adequate response towards IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all possible levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in disease tolerance to sepsis. In conclusion, hepatic HNF4α fails in sepsis, causing PPARα downregulation and metabolic problems and a disturbed IL6-mediated acute phase response. The data open new insights and therapeutic options in sepsis.

Published in

A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death

Van Dender C, Timmermans S, Paakinaho V et al. · EMBO molecular medicine 2024 · PMID 39261648 · doi:10.1038/s44321-024-00130-1

This dataset

Open GSE260635 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 GSE260635_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 PRJNA1082376 and SRA study SRP492690. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39261648) ↗

Study design

4 × liver, KO CLP, vs 4 × liver, KO SHAM, vs 4 × liver, WT CLP, vs 4 × liver, WT SHAM,

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM8121351 liver, KO CLP, rep1 liver, KO CLP,
GSM8121352 liver, KO CLP, rep2 liver, KO CLP,
GSM8121353 liver, KO CLP, rep3 liver, KO CLP,
GSM8121354 liver, KO CLP, rep4 liver, KO CLP,
GSM8121355 liver, KO SHAM, rep1 liver, KO SHAM,
GSM8121356 liver, KO SHAM, rep2 liver, KO SHAM,
GSM8121357 liver, KO SHAM, rep3 liver, KO SHAM,
GSM8121358 liver, KO SHAM, rep4 liver, KO SHAM,
GSM8121359 liver, WT CLP, rep1 liver, WT CLP,
GSM8121360 liver, WT CLP, rep2 liver, WT CLP,
GSM8121361 liver, WT CLP, rep3 liver, WT CLP,
GSM8121362 liver, WT CLP, rep4 liver, WT CLP,
GSM8121363 liver, WT SHAM, rep1 liver, WT SHAM,
GSM8121364 liver, WT SHAM, rep2 liver, WT SHAM,
GSM8121365 liver, WT SHAM, rep3 liver, WT SHAM,
GSM8121366 liver, WT SHAM, rep4 liver, WT SHAM,

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GSE260577 A critical role for Hepatocyte Nuclear Factor 4 alpha in polymicrobial sepsis-associated metabolic reprogramming and death: H3K27ac and H3K4me3 after CLP sepsis model 18 samples shares clp, sepsis-associated, polymicrobial, reprogramming, hepatocyte, critical
GSE319754 RXRα Suppression Drives Hepatic Metabolic and Immune Dysfunction in Sepsis: Gene induction by BEX in Sham & CLP (8h) 12 samples shares sham, clp
GSE319852 RXRα Suppression Drives Hepatic Metabolic and Immune Dysfunction in Sepsis: RXRα KO in CLP/SHAM 12 samples shares sham, clp
GSE275526 snRNA sequencing on the kidney tissue of cecal ligation and puncture (CLP) and Sham mice. 6 samples shares sham, clp
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GSE275479 snRNA sequencing on the brain tissue of cecal ligation and puncture (CLP) and Sham mice. 6 samples shares sham, clp
GSE275689 snRNA sequencing on the liver tissue of cecal ligation and puncture (CLP) and sham mice 6 samples shares sham, clp
GSE186822 Transcriptomic Profiling on Kidneys of Mice after Cecal Ligation and Puncture (CLP) Compared to Sham Operation 5 samples shares sham, clp

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