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Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion

GSE300981 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2025/06/30 Platform GPL30172
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: 4 × Mouse liver ChIP TBX3 biol vs 4 × Mouse liver ChIP IgG control biol vs 3 × H2.35 mouse cell line CUT&RUN (Tbx3-V5) biolGroups 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
Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretionThe Journal of clinical investigation · 2025
Summary (written by the submitters)
We’ve previously demonstrated that hepatocytes with Tbx3 deletions have increased cellular fitness and clonally expand during metabolic-dysfunction associated steatotic liver disease (MASLD) development. TBX3 is a transcription factor that is critical for embryonic development, but has never been studied within the context of MASLD. Here, we show that somatic mutations in TBX3 are found in human patients with MASLD.
Read the full summary ↓
Liver specific deletion of Tbx3 in mice protects against diet induced MASLD through upregulating VLDL-TG particle secretion. TBX3 transcriptionally suppresses the conventional secretory pathway and cholesterol biosynthesis. Hdlbp is a direct target of TBX3 that is responsible for altered VLDL secretion. In contrast to WT TBX3, TBX3 harboring somatic mutations found in humans failed to suppress VLDL secretion in vivo. In conclusion, mutations in TBX3 promote clonal expansion during MASLD development through increased lipid disposal, demonstrating clonal fitness can benefit the liver even at the cost of hyperlipidemia.
Published in
Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion
Mannino G, Quinn G, Zhu M et al. · The Journal of clinical investigation 2025 · PMID 40638249 · doi:10.1172/JCI191855
This dataset
Open GSE300981 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE300981_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 peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1282776 and SRA study SRP595013. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40638249) ↗
Study design
4 × Mouse liver ChIP TBX3 biol vs 4 × Mouse liver ChIP IgG control biol vs 3 × H2.35 mouse cell line CUT&RUN (Tbx3-V5) biol

Supports a between-group comparison across 11 samples.

How we read this: 3 replicated groups read from 12 sample titles; they account for 11 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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