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Oncogenic MAPK signalling induces epithelial cell state change and therapeutic resistance in vivo [RNA-Seq]

GSE307773 Mus musculus (mouse) RNA-seq (gene expression) 175 samples Submitted 2025/09/16 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 175 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
175 samples: 20 conditions, mostly with about 10 replicates eachGroups 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
MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistanceNature · 2026
Summary (written by the submitters)
The colorectal epithelium is a rapidly renewing tissue, with a remarkable capacity to regenerate following injury. In colorectal cancer (CRC), this regenerative capacity can be co-opted to drive epithelial plasticity. Activation of oncogenic MAPK signalling in CRC is common, with mutations frequently found in both KRAS (40-50%) and BRAF (10%), alongside other mechanisms of EGFR pathway upregulation.
Read the full summary ↓
Nonetheless, inhibition of this pathway is often linked to rapid therapeutic resistance in patients. Given the recent development of KRAS inhibitors and the licensing of BRAF+EGFR inhibitor combinations we have investigated mechanisms of resistance to these agents in complex mouse models of CRC. Here we show that MAPK signalling supports the regenerative/revival stem cell phenotype in vivo, while its inhibition leads to rapid remodelling of both Kras and Braf mutant mouse models to a high Wnt activity canonical stem cell phenotype marked by expression of Lgr5. This results in acute therapeutic resistance in Kras driven, and delayed resistance in Braf driven models. Importantly, where therapeutic MAPK targeting is applied in the presence of a single regenerative epithelial population, such as early metastatic disease, or where plasticity is restrained, for example through Wnt pathway restriction, a marked impact on tumourigenesis is observed. Modelling of an BRAF and RNF43-mutant patient population, clinically super-responders to BRAF/EGFR inhibitor therapy, demonstrates excellent response to therapy due to restricted epithelial plasticity, highlighting the criticality of cellular plasticity in therapeutic response. Together, our data provide clear insight into the mechanisms underpinning resistance to targeting oncogenic MAPK signalling in CRC. Moreover, we demonstrate that strategies that aim to restrict epithelial plasticity or corral into or intervene when tumours are in a regenerative cell fate may improve efficacy of MAPK targeting agents in CRC.
Published in
MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistance
White M, Mills ML, Millett LM et al. · Nature 2026 · PMID 41286180 · doi:10.1038/s41586-025-09916-w
This dataset
Open GSE307773 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 GSE307773_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 PRJNA1327309 and SRA study SRP620242. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41286180) ↗
Study design
20 conditions, mostly with about 10 replicates each
BPN SI Tumour ×30 BPNA Colon Tumour Vehicle ×16 Apc Colon Tumour ×13 BPNA Colon Tumour ×12 BPA Colon Tumour ×10 BPRNF SI Tumour, Dabrafenib-Erlotinib Treated ×10 BPRNF SI Tumour Vehicle ×10 AK Colon Tumour ×9 +12 more

Supports a between-group comparison across 175 samples.

How we read this: 20 replicated groups read from 175 sample titles; they account for 175 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

+ 135 more — browse all 175 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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