GEO series

A critical role for Hepatocyte Nuclear Factor 4 alpha in polymicrobial sepsis-associated metabolic reprogramming and death: H3K27ac and H3K4me3 after CLP sepsis model

GSE260577 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 18 samples Submitted 2024/03/12 Platform GPL19057

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 18 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Mus musculus (mouse)
Samples: 18 samples: 4 × liver, H3K27ac, CLP vs 4 × liver, H3K4me3, CLP vs 4 × liver, H3K27ac, Sham vs 4 × liver, H3K4me3, ShamGroups 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)

Sepsis is a maladaptive host response towards an infection leading to tissue damage, organ failure, and ultimately death. In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is hindered by hepatic disappearance of the key transcription factor PPARα. Since PPARα acts as a central player in intracellular catabolism of fatty acids (FAs), sepsis results in excess free FAs, which cause lipotoxicity.

Read the full summary ↓

The mechanism upstream of the PPARα downregulation in sepsis is unknown. A potential mechanism resides in HNF4α, which regulates liver lipid metabolism directly by activating Ppara gene expression and indirectly by interacting with PPARα itself. A proper functioning of HNF4α is essential for maintaining liver identity. We here show that sepsis causes a progressive HNF4α loss-of-function in the liver, which impacts expression of several nuclear receptors, among which PPARα, and is characterized by a reduced HNF4α DNA binding. Specific HNF4α depletion in the liver dramatically worsens sepsis lethality, associated with increased steatosis and hepatocyte damage. HNF4α dysfunction also prevents an adequate response towards IL6, controlled by CEBPβ and STAT3, which is critical for a proper liver regeneration and survival. In addition, the HNF4α agonist NCT partially protects against sepsis by limiting hepatic steatosis and liver dysfunction. In conclusion, hepatic HNF4α fails in sepsis, causing PPARα downregulation and consequent metabolic problems on the one hand, and a disturbed IL6-mediated acute phase response and regeneration on the other hand. 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 GSE260577 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE260577_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1082262 and SRA study SRP492569. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39261648) ↗

Study design

4 × liver, H3K27ac, CLP vs 4 × liver, H3K4me3, CLP vs 4 × liver, H3K27ac, Sham vs 4 × liver, H3K4me3, Sham

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 18 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

GSM8119657 liver, H3K27ac, CLP rep1 liver, H3K27ac, CLP
GSM8119658 liver, H3K27ac, CLP rep2 liver, H3K27ac, CLP
GSM8119659 liver, H3K27ac, CLP rep3 liver, H3K27ac, CLP
GSM8119660 liver, H3K27ac, CLP rep4 liver, H3K27ac, CLP
GSM8119661 liver, H3K4me3, CLP rep1 liver, H3K4me3, CLP
GSM8119662 liver, H3K4me3, CLP rep2 liver, H3K4me3, CLP
GSM8119663 liver, H3K4me3, CLP rep3 liver, H3K4me3, CLP
GSM8119664 liver, H3K4me3, CLP rep4 liver, H3K4me3, CLP
GSM8119665 liver, H3K27ac, Sham rep1 liver, H3K27ac, Sham
GSM8119666 liver, H3K27ac, Sham rep2 liver, H3K27ac, Sham
GSM8119667 liver, H3K27ac, Sham rep3 liver, H3K27ac, Sham
GSM8119668 liver, H3K27ac, Sham rep4 liver, H3K27ac, Sham
GSM8119669 liver, H3K4me3, Sham rep1 liver, H3K4me3, Sham
GSM8119670 liver, H3K4me3, Sham rep2 liver, H3K4me3, Sham
GSM8119671 liver, H3K4me3, Sham rep3 liver, H3K4me3, Sham
GSM8119672 liver, H3K4me3, Sham rep4 liver, H3K4me3, Sham
GSM8119673 liver, Sham, input
GSM8119674 liver, CLP, input

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