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Physiological YAP activation alleviate ER stress to mitigate alcohol-induced liver damage by promoting ATF6 transcriptional activation

GSE339349 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2026/07/25 Platform GPL33326
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.
Summary (written by the submitters)
Alcohol-associated liver disease (ALD) is a major global health concern driven by chronic metabolic stress. Alcohol-induced ER stress is an early event in hepatocytes, which disrupts lipid metabolism and contributes to hepatic steatosis and inflammation, driving liver damage during the progression of ALD and other liver disorders. Here, we report that in a mouse chronic alcohol feeding model, YAP activity in the liver is reduced at early stages of alcohol exposure, primarily by ER stress-induced Unfolded Protein Response (UPR), independently of canonical Hippo kinase activities.
Read the full summary ↓
We further found that YAP activity is reduced, with elevated ER stress in human ALD. We demonstrated that genetic deletion of Yap in hepatocytes exacerbates ALD, while overexpression or pharmacological activation of the wild-type (WT) YAP alleviates ALD and ER stress. The protective role of physiological YAP activation in reducing ER-stress-induced hepatic damage is further demonstrated by a substantial rescue of liver function and viability severely compromised by acetaminophen overdose. This is in sharp contrast to pathological YAP hyperactivation that occurs later in alcohol exposure, which exacerbates disease progression in alcoholic hepatitis (AH). Mechanistically, we show that transcriptional activation of Activating Transcription Factor 6 (ATF6), a key transmembrane ER stress sensor that also serves as a transcription factor after ER stress-induced cleavage. We found that ATF6 transcription activity is both necessary and sufficient to mediate the protective role of YAP in ER stress and alcohol induced liver injury, through its target genes Manf and Hspa5 (Grp78). YAP potentiates the ATF6 transcription activity in a TEAD-dependent manner. Our study identifies an ATF6-dependent protective role of YAP in maintaining ER homeostasis, which can be leveraged to prevent or treat ALD and other liver diseases.
This dataset
Open GSE339349 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 GSE339349_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 PRJNA1498487. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 conditions, mostly in triplicate
Liver, Pair-fed, control, ×3 Liver, EtOH-fed, control, ×3 Liver, Pair-fed, Hepatocyte-specific Yap knoc… ×3 Liver, EtOH-fed, Hepatocyte-specific Yap knoc… ×3 Liver, Pair-fed, Hepatocyte-specific YAP over… ×3 Liver, EtOH-fed, Hepatocyte-specific YAP over… ×3

Supports a case/control comparison: 12 samples read as cases, 6 as controls.

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
Datasets on a similar topic

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