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Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis [PROX1 CUT&RUN Liver/MEF/Hep3B]

GSE284653 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 22 samples Submitted 2024/12/18 Platform GPL21626Platform GPL21697
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 22 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
Homo sapiens (human)
Samples
22 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.
Paper
Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesisNature genetics · 2025
Summary (written by the submitters)
Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here, we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong.
Read the full summary ↓
We validated hepatocyte-specific candidates using reprogramming, revealing that Prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternative fate master regulators. In mice, Prox1 was required for efficient hepatocyte regeneration after injury and was sufficient to prevent liver tumorigenesis. In line with patient data, Prox1 depletion caused hepatocyte fate loss in vivo and enabled the transition of hepatocellular carcinoma to cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma to hepatocellular carcinoma transdifferentiation. Our findings provide evidence for PROX1 as a hepatocyte-specific safeguard and support a model where cell type-specific repressors actively suppress plasticity throughout life to safeguard lineage identity and thus prevent disease.
Published in
Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis
Lim B, Kamal A, Gomez Ramos B et al. · Nature genetics 2025 · PMID 39948437 · doi:10.1038/s41588-025-02081-w
This dataset
Open GSE284653 in finder → Find more 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 GSE284653_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 PRJNA1199996 and SRA study SRP552484. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39948437) ↗
Study design
6 conditions, mostly in triplicate
Liver Prox1 ×5 Liver IgG ×5 Hep3B Flag ×3 Hep3B IgG ×3 MEF Flag ×3 MEF IgG ×3

Supports a between-group comparison across 22 samples.

How we read this: 6 replicated groups read from 22 sample titles; they account for 22 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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