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Inter-organ transmission of hepatocellular senescence induces multi-organ dysfunction through the TGFbeta signalling pathway

GSE267196 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2024/08/23 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 5 conditions, mostly with about 4 replicates eachGroups 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
Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβNature cell biology · 2024
Summary (written by the submitters)
Cellular senescence is associated with aging but also impacts various physiological and pathological processes such as embryonic development and wound healing. Factors secreted by senescent cells can affect their microenvironment, including local spreading of senescence. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure.
Read the full summary ↓
Why the latter occurs is poorly understood however, the presence of hepatic senescence is associated with poor prognosis and extrahepatic organ failure in acute liver disease. Here, using genetic mouse models of hepatocyte-specific senescence, we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence. In patients with acute indeterminate hepatitis, the extent of hepatocellular senescence predicts the occurrence of extrahepatic dysfunction, need for liver transplantation and mortality. We identify the Transforming Growth Factor Beta (TGFbeta) pathway as a critical mediator of systemic spread of senescence and TGFbeta inhibition blocks senescence transmission to other organs preventing renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence which, independent of aging, contributes to multi-organ dysfunction.
Published in
Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ
Kiourtis C, Terradas-Terradas M, Gee LM et al. · Nature cell biology 2024 · PMID 39537753 · doi:10.1038/s41556-024-01543-3
This dataset
Open GSE267196 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 GSE267196_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 PRJNA1110225 and SRA study SRP507030. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39537753) ↗
Study design
5 conditions, mostly with about 4 replicates each
Mouse Kidney, Mdm2 Ex 5/6, Untreated Control, ×4 Mouse Kidney, Mdm2 Ex 5/6, AAV8-Control2, ×4 Mouse Kidney, Mdm2 Ex 5/6, AAV8-Control4, ×4 Mouse Kidney, Mdm2 Ex 5/6, AAV8-Cre4, ×4 Mouse Kidney, Mdm2 Ex 5/6, AAV8-Cre2, ×4

Supports a between-group comparison across 20 samples.

How we read this: 5 replicated groups read from 20 sample titles; they account for 20 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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