GEO series

Oncogenic Kras cells override homeostatic cell elimination mechanisms in adult pancreas via Wnt signalling and cell dormancy.

GSE255283 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/10/02 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 3 × WT vs 3 × KC vs 3 × PC vs 3 × KPCGroups 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: KRASG12D Cells Override Homeostatic Cell Elimination Mechanisms in Adult Pancreas Via Wnt5a and Cell DormancyGastroenterology · 2025

Summary (written by the submitters)

Epithelial tissues use homeostatic defence mechanisms to actively remove aberrant or poorly functioning cells and maintain tissue health. We show that when present in tissues in low numbers, cells expressing KrasG12D or p53R172H mutations compete with normal cells for survival and are often eliminated. This implies that tumour initiation would require mechanisms whereby mutant cells override tissue homeostasis and remain in a tissue; however, the biology of these initial events is poorly understood.

Read the full summary ↓

Here, we use an in vivo model of sporadic tumorigenesis in the adult pancreas to show that cell elimination processes are inefficient and a proportion of KrasG12D or p53R172H expressing cells are never eliminated from the epithelium. Using RNA sequencing of non-eliminated mutant populations, we reveal a general activation of the non-canonical Wnt pathway. We demonstrate that non-eliminated KrasG12D cells express cell dormancy and diapause gene signatures, suggesting non-eliminated KRasG12D cells adopt a dormant cell state in vivo. Using cell competition assays in vitro, we show that active Wnt or cell cycle arrest blocks elimination of RasV12 mutant cells from normal epithelial cell sheets. Importantly, we demonstrate that Wnt signalling is a general mechanism required to promote retention of KrasG12D and p53R172H cells in tissues in vivo . Our results suggest that mutant cells activate Wnt and/or a dormant cell state to avoid homeostatic tissue defence mechanisms and survive in the adult pancreas.

Published in

KRASG12D Cells Override Homeostatic Cell Elimination Mechanisms in Adult Pancreas Via Wnt5a and Cell Dormancy

Salvador-Barbero B, Alatsatianos M, Morton JP et al. · Gastroenterology 2025 · PMID 40204099 · doi:10.1053/j.gastro.2025.02.042

This dataset

Open GSE255283 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 GSE255283_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 PRJNA1074363 and SRA study SRP488739. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40204099) ↗

Study design

3 × WT vs 3 × KC vs 3 × PC vs 3 × KPC

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

GSM8068147 WT1 WT
GSM8068148 WT2 WT
GSM8068149 WT3 WT
GSM8068150 KC2 KC
GSM8068151 KC3 KC
GSM8068152 KC4 KC
GSM8068153 PC1 PC
GSM8068154 PC2 PC
GSM8068155 PC3 PC
GSM8068156 KPC1 KPC
GSM8068157 KPC2 KPC
GSM8068158 KPC3 KPC

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