GEO series

Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11 [MeRIP-m6A]

GSE266228 Mus musculus (mouse) DNA methylation 16 samples Submitted 2024/08/14 Platform GPL21103

At a glance

DNA methylation · mouse · 16 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Mus musculus (mouse)
Samples: 16 samples
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)

Nonalcoholic fatty liver disease (NAFLD) including its more severe manifestation, nonalcoholic steatohepatitis (NASH), is a global public health challenge with no approved pharmacological therapies. Here, we reveal an indispensable role for the deubiquitinating enzyme RPN11 in the development of NAFLD and NASH. Ablation of hepatic RPN11 markedly protected mice from several diets-induced liver steatosis, insulin resistance and steatohepatitis, whereas RPN11 overexpression had the opposite effects.

Read the full summary ↓

Mechanistically, RPN11 interacts with and stabilizes METTL3 via deubiquitination initiated at lysine 241, to increase the m6A modification and expression of acyl-CoA synthetase short chain family member 3 (Acss3). RPN11-Acss3 axis generates propionyl-CoA and functions in histone propionylation to transcriptionally upregulate lipid metabolism-related genes. Of pathophysiological significance, RPN11-METTL3-Acss3-histone propionylation modification pathway is activated in the livers of patients with NAFLD and positively correlated with hepatic triglyceride contents. More importantly, pharmacological inhibition of RPN11 by Capzimin showed dramatic beneficial effects in ameliorating NAFLD, NASH and related metabolic disorders in mice. Capzimin also reduces intracellular lipid contents in human primary hepatocytes cultured in 2D and 3D spheroids. Together, these results demonstrate that RPN11 is essential for the development of NAFLD/NASH and that suppressing RPN11 has therapeutic potential for the treatment.

This dataset

Open GSE266228 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 GSE266228_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 beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1106417 and SRA study SRP504922. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 16 more — browse all 16 samples with per-sample file links →

Datasets on a similar topic

GSE263831 Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11 [mRNA-seq] 16 samples shares rpn11, deubiquitylating, amelioration, nonalcoholic, inhibiting, enzyme, fatty
GSE263875 Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11 (mRNA-seq db vs. lean) 8 samples shares rpn11, deubiquitylating, amelioration, nonalcoholic, inhibiting, enzyme, fatty
GSE262801 Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11 4 samples shares rpn11, deubiquitylating, amelioration, nonalcoholic, inhibiting, enzyme, fatty
GSE299691 Sex-dependent amelioration of laser-induced choroidal neovascularization by Short-Chain Fatty Acid treatment in a mouse model 43 samples shares amelioration, fatty
GSE325653 Transcriptomic sequencing reveals gene expression profiles underlying photobiomodulation-mediated amelioration of hypobaric hypoxia-induced synaptic plasticity deficits in mice 10 samples shares amelioration
GSE274942 AAV-mediated silencing of Sox4 leads to long-term amelioration of liver phenotypes in mouse models of Alagille syndrome (scRNA-Seq) 4 samples shares amelioration

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