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Analysis of heterogeneity within genetic murine models of HCC

GSE276089 Mus musculus (mouse) RNA-seq (gene expression) 19 samples Submitted 2024/12/03 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 19 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
19 samples: 13 × Mouse Liver Ctnnb1-tmtMmt, MYC, Tumou vs 3 × Mouse Liver Ctnnb1-tmtMmt, MYC, Control vs 3 × Mouse Liver Ctnnb1-tmtMmt, MYC, Control High AAVGroups 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
Human-correlated genetic models identify precision therapy for liver cancerNature · 2025
Summary (written by the submitters)
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer related mortality worldwide1,2. HCC occurs typically from a background of chronic liver disease, caused by a spectrum of predisposing conditions. Tumour development is driven by the expansion of clones that accumulated progressive driver mutations3, with hepatocytes the most likely cell of origin2.
Read the full summary ↓
However, the landscape of driver mutations in HCC is independent of the underlying aetiologies4. Despite an increasing range of systemic treatment options for advanced HCC outcomes remain heterogeneous and typically poor. Emerging data suggest that drug efficacies depend on disease aetiology and genetic alterations5,6. Exploring subtypes in preclinical models with human relevance will therefore be essential to advance precision medicine in HCC7. We generated over twenty-five new genetically-driven in vivo and in vitro HCC models. Our models represent multiple features of human HCC, including clonal origin, histopathological appearance, and metastasis to distant organs. We integrated transcriptomic data from the mouse models with human HCC data and identified four common human-mouse subtype clusters. The subtype clusters had distinct transcriptomic characteristics that aligned with histopathology. In a proof-of-principle analysis, we verified response to standard of care treatment and used a linked in vitro-in vivo pipeline to identify a promising therapeutic candidate, cladribine, that has not been linked to HCC treatment before. Cladribine acts in a highly effective subtype-specific manner in combination with standard of care therapy.
Published in
Human-correlated genetic models identify precision therapy for liver cancer
Müller M, May S, Hall H et al. · Nature 2025 · PMID 39972137 · doi:10.1038/s41586-025-08585-z
This dataset
Open GSE276089 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 GSE276089_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 PRJNA1154667 and SRA study SRP529689. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39972137) ↗
Study design
13 × Mouse Liver Ctnnb1-tmtMmt, MYC, Tumou vs 3 × Mouse Liver Ctnnb1-tmtMmt, MYC, Control vs 3 × Mouse Liver Ctnnb1-tmtMmt, MYC, Control High AAV

Supports a between-group comparison across 19 samples.

How we read this: 3 replicated groups read from 19 sample titles; they account for 19 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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