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A Mouse Model for Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatocellular Carcinoma [ATAC-seq]

GSE246213 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/06/17 Platform GPL21273
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 12 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
12 samples: 3 × ATAC-seq of control SCD fed mice without STZ treatment, 20w, biological replication vs 3 × ATAC-seq of STZ+ SCD mice, 20w, biological replication vs 3 × ATAC-seq of HFD fed mice without STZ treatment, 20w, biological replication vs 3 × ATAC-seq of STZ+HFD model, 20w, biological replicationGroups 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 male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinomaNature communications · 2024
Summary (written by the submitters)
The lack of an appropriate preclinical model of non-alcoholic fatty liver disease (NAFLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Therefore, we developed new mose model with Streptozotocin (STZ)and high-fat diet (HFD). In breif, male C57BL/6J mice were injected with low-dose streptozotocin (40 mg/kg) for 5 consecutive days beginning at 7 weeks of age and subsequently fed a high-fat diet from week 8 (STZ+HFD) onwards.
Read the full summary ↓
Hepatic histopathology, transcriptomics, epigenetics, and metabolic phenotypes were evaluated at various time-points. The hepatic transcriptomes of STZ+HFD mice and NAFLD patients with similar liver histopathology were compared. In STZ+HFD mice, dietary changes from HFD to standard chow and administration of tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, were introduced to assess the therapeutic efficacy of these interventions. STZ+HFD mice gradually developed fatty liver, non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. In particular, from 32 weeks of age, NASH and advanced fibrosis were evident. At 38 weeks, a proportion of STZ+HFD mice developed HCC, which was subsequently observed in all mice up to 68 weeks of age. Furthermore, the hepatic transcriptomic features of STZ+HFD mice closely reflected those of patients with NASH and NAFLD-related HCC. Notably, dietary changes and tirzepatide administration alleviated NASH, hepatic fibrosis, and hepatic tumorigenesis in STZ+HFD mice. Put together, we established a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in NAFLD patients with metabolic dysfunction was successfully established.
Published in
A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma
Jeong BK, Choi WI, Choi W et al. · Nature communications 2024 · PMID 39090079 · doi:10.1038/s41467-024-50660-y
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 GSE246213_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1032056 and SRA study SRP468350. Searching any of these in the dataset finder brings you back here.

Study design
3 × ATAC-seq of control SCD fed mice without STZ treatment, 20w, biological replication vs 3 × ATAC-seq of STZ+ SCD mice, 20w, biological replication vs 3 × ATAC-seq of HFD fed mice without STZ treatment, 20w, biological replication vs 3 × ATAC-seq of STZ+HFD model, 20w, biological replication

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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