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Differential squamous cell fates elicited by NRF2 gain-of-function versus KEAP1 loss-of-function

GSE255927 Mus musculus (mouse) RNA-seq (gene expression) 25 samples Submitted 2024/03/22 Platform GPL28457
At a glance

RNA-seq (gene expression) · mouse · 25 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
25 samples: 12 × K5CreERT2 vs 6 × K5Cre_E vs 4 × Esophagus, K5CreERT2, Wild-Type vs 3 × Esophagus, K5Cre, Wild-Type_EGroups 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
Differential squamous cell fates elicited by NRF2 gain of function versus KEAP1 loss of functionCell reports · 2024
Summary (written by the submitters)
Clinical evidence has revealed that high-level activation of NRF2 caused by somatic mutations in NRF2 is frequently detected in esophageal squamous cell carcinoma (ESCC), whereas that by somatic mutations in KEAP1, a negative regulator of NRF2, is not. Here, we challenged to generate a mouse model of NRF2-activated ESCC using the cancer-derived NRF2L30F mutation and cancer-driver mutant Trp53R172H.
Read the full summary ↓
Concomitant expression of NRF2L30F and Trp53R172H induced proliferation of squamous cell epithelia and resulted in NRF2-activated ESCC-like lesions. In contrast, while squamous cell-specific deletion of KEAP1 induced similar NRF2 hyper-activation, the loss-of-KEAP1 combined with Trp53R172H did not elicit the proliferation and formation of ESCC-like lesions. Instead, KEAP1-deleted cells disappeared from the esophageal epithelium over time by cell competition. These findings provide insights into the observation that somatic mutations are more frequently observed in NRF2 than in KEAP1, and the mouse model developed here will be instrumental in elucidating the mechanistic basis leading to NRF2-activated ESCC.
Published in
Differential squamous cell fates elicited by NRF2 gain of function versus KEAP1 loss of function
Takahashi J, Suzuki T, Sato M et al. · Cell reports 2024 · PMID 38602872 · doi:10.1016/j.celrep.2024.114104
This dataset
Open GSE255927 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 GSE255927_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 PRJNA1077254 and SRA study SRP489982. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38602872) ↗
Study design
12 × K5CreERT2 vs 6 × K5Cre_E vs 4 × Esophagus, K5CreERT2, Wild-Type vs 3 × Esophagus, K5Cre, Wild-Type_E

Supports a between-group comparison across 25 samples.

How we read this: 4 replicated groups read from 25 sample titles; they account for 25 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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