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The oncogenic potential of YAP requires Y357 phosphorylation in cholangiocytes but not in hepatocytes

GSE297845 Mus musculus (mouse) Single-cell RNA-seq 18 samples Submitted 2025/12/31 Platform GPL21103
At a glance

Single-cell RNA-seq · mouse · 18 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
18 samples: 6 × YAP-S_M vs 6 × YAP-SY_M vs 3 × SB1 vs 3 × SY1Groups 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
The oncogenic potential of YAP requires Y357 phosphorylation in cholangiocytes but not in hepatocytesCellular oncology (Dordrecht, Netherlands) · 2025
Summary (written by the submitters)
The transcriptional cofactor yes-associated protein (YAP) functions as a proto-oncogene and a key effector of the canonical Hippo pathway. Phosphorylation at serine 127 (S127) by core Hippo kinases inhibits YAP activity, while phosphorylation at tyrosine 357 (Y357) by SRC-family kinases promotes its activation. YAP activation has been implicated in many cancers, including primary liver cancers (PLCs).
Read the full summary ↓
Owing to the inherent plasticity of the liver, PLCs may arise from different cells of origin. However, it is unknown whether the level of YAP activation favors liver tumorigenesis from specific cells of origin or instead promotes lineage commitment in a single cell of origin across the PLC spectrum. To assess the role of YAP tyrosine phosphorylation in liver tumorigenesis, C57BL/6 mice underwent biliary transfection with the Sleeping Beauty transposon system to deliver myr-AKT and YAP S127A (YAP-S) or YAP S127A/Y357F (YAP-SY). While YAP-S mice represent an established model of intrahepatic cholangiocarcinoma (iCCA), unexpectedly, a shift in tumor phenotype to hepatocellular carcinoma (HCC) was identified in YAP-SY mice. Transcriptome and pathway analysis revealed differential activation of cytokines and growth factors (e.g., TGFB1, TNF, IL1B, IL4, and INFG) and transcription factors (e.g., STAT3, PGR, AHR, STAT1, and NFKB) associated with this phenotypic switch. To determine the cell of origin, tumors were generated in lineage tracing mice (ROSA26mT/mG mice treated with AAV8-TBG-Cre), which demonstrated that HCC originated from hepatocytes and iCCA from cholangiocytes in the biliary transfection model. Finally, two tumor-derived cell lines with YAP-SY and constitutive AKT expression were isolated, representing a novel, transplantable murine syngeneic model with mixed features of HCC and iCCA.
Published in
The oncogenic potential of YAP requires Y357 phosphorylation in cholangiocytes but not in hepatocytes
Aksu MD, Millender JT, McCabe CE et al. · Cellular oncology (Dordrecht, Netherlands) 2025 · PMID 41442017 · doi:10.1007/s13402-025-01133-x
This dataset
Open GSE297845 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 GSE297845_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1266417 and SRA study SRP587445. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41442017) ↗
Study design
6 × YAP-S_M vs 6 × YAP-SY_M vs 3 × SB1 vs 3 × SY1

Supports a between-group comparison across 18 samples.

How we read this: 4 replicated groups read from 18 sample titles; they account for 18 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
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