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Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution. [RNA-Seq]

GSE312828 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2026/04/12 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 6 conditions, mostly with about 4 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
Lineage plasticity of the integrated stress response is a hallmark of cancer evolutionbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Tumour progression towards dedifferentiated cell clusters plays a critical role in intratumour heterogeneity and therapy resistance. While tumour microenvironmental stress has been implicated, the underlying mechanisms remain poorly defined. Using mouse models of lung adenocarcinoma, we demonstrate that activation of the integrated stress response (ISR)—marked by phosphorylation of eIF2 (p-eIF2) and ATF4 induction—drives tumour heterogeneity.
Read the full summary ↓
ISR activation facilitates the emergence of high-plasticity, undifferentiated and pre-epithelial-to-mesenchymal transition clusters characterized by elevated ATF4 and MYC activity. This process is MYC dependent and involves ISR-mediated repression of NKX2-1, a key determinant of alveolar identity, and induction of CHCHD10, a regulator of mitochondrial integrity and metabolic fitness. Disruption of the p-eIF2–ATF4 axis induces mitochondrial dysfunction, limits dedifferentiation and suppresses tumour growth. In human lung adenocarcinoma, ISR-driven dedifferentiation correlates with advanced disease and poor prognosis, identifying the ISR as a central driver of lineage reprogramming and metabolic fitness in tumour progression.
Published in
Lineage plasticity of the integrated stress response is a hallmark of cancer evolution
Diao S, Zou JY, Wang S et al. · bioRxiv : the preprint server for biology 2025 · PMID 39990365 · doi:10.1101/2025.02.10.637516
This dataset
Open GSE312828 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 GSE312828_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 PRJNA1377485 and SRA study SRP653277. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39990365) ↗
Study design
6 conditions, mostly with about 4 replicates each
eIF2αS/S cells, shControl, ×4 eIF2αS/S cells, shAtf4, ×4 eIF2αS/S cells, siControl, ×4 eIF2αS/S cells, siChchd10, ×4 eIF2αA/A cells, siControl, ×4 eIF2αA/A cells, siChchd10, ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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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