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ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injury

GSE254747 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2024/06/01 Platform GPL28330
At a glance

RNA-seq (gene expression) · mouse · 18 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
18 samples: 6 conditions, mostly in triplicateGroups 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
ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injuryThe Journal of clinical investigation · 2024
Summary (written by the submitters)
Abstract Background & Aims: In liver transplantation, steatotic donor livers are rapidly increasing but are more susceptible to ischemia-reperfusion (I/R) injury. This study aimed to investigate the underlying mechanisms and identify therapeutic targets. Methods: Cell death markers were determined in donor livers and animal models.
Read the full summary ↓
Casp8f/f;Alb-Cre, Ripk1D138N/D138N, Tnf-/-, Ripk3-/-, Trif-/-, Zbp1-/- mice were fed high fat diet or choline-deficient high fat diet to induce steatotic livers and were then subjected to I/R injury to investigate the mechanisms of cell death and inflammation. Primary mouse or human hepatocytes were isolated and subjected to hypoxia-reoxygenation challenge to further elucidate the regulation mechanisms. Results: Apoptosis- and inflammation-induced injury was exacerbated in I/R process of steatotic livers, with inflammation-induced injury playing a more predominant role. In both normal and steatotic livers, caspase-8 ablation mitigated I/R injury by reducing apoptosis but not inflammation while RIPK1 kinase inhibition more effectively protected against I/R injury by alleviating both apoptosis and inflammation. Z-DNA binding protein 1 (ZBP1) but not TNF-α deficiency inhibited RIPK1 activation and protected against I/R injury in steatotic livers but not normal livers. In steatotic livers, overmuch palmitic acid triggered ZBP1 transcription through activating JNK pathway. During liver transplantation, excessive reactive oxygen species were generated during I/R injury and triggered ZBP1 oligomerization, which led to the kinase activation of RIPK1 and the subsequent aggravation of apoptosis- and inflammation-induced injury. Conclusions: ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver I/R injury, which could be leveraged to protect steatotic donor livers in transplantation.
Published in
ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injury
Liu R, Cao H, Zhang S et al. · The Journal of clinical investigation 2024 · PMID 38743492 · doi:10.1172/JCI180451
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 GSE254747_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 PRJNA1071611 and SRA study SRP487217. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
Zbp1_WT ×3 Zbp1_KO ×3 Vector_Vehicle ×3 Zbp1_Vehicle ×3 Vector_Nec1s ×3 Zbp1_Nec1s ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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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