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KDM8 is a master regulator for hypoxia-induced metastatic heterogeneity in pancreatic cancer [Bulk RNA-Seq]

GSE304599 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/12/04 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 16 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
16 samples: 8 conditions, mostly in duplicateGroups 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
Hypoxia-induced metastatic heterogeneity in pancreatic cancerResearch square · 2025
Summary (written by the submitters)
This study aims to elucidate how hypoxia promotes pancreatic cancer metastasis by suppressing the JmjC-containing histone lysine demethylase KDM8. In solid tumors, hypoxia is a key factor that reprograms cancer cells into a highly metastatic state. Hypoxia is a well-established inducer of epithelial-to-mesenchymal transition, which is associated with treatment resistance and metastasis.
Read the full summary ↓
In addition, hypoxia promotes chromosomal instability - a hallmark of cancer and a key contributor to metastasis. Despite this, the mechanisms by which cancer cells simultaneously hijack these elements of hypoxic adaptation to promote metastasis remains unknown. We found that CRISPR-mediated targeting of Kdm8 in a genetically engineered mouse model of pancreatic ductal adenocarcinoma rewires the cancer cell transcriptomic programs, leading to a profound loss of the differentiated morphology and widespread metastatic disease. Importantly, Kdm8 suppression in normoxia recapitulates major aspects of the global epigenetic changes and the transcriptomic rewiring induced by hypoxia. Further, Kdm8 deficiency leads to mitotic defects, increased micronuclei formation, Kras copy number gains, and enhanced chromosomal instability. Notably, disruption of the demethylase function of KDM8 phenocopies the effects of KDM8 loss, whereas expression of hypermorphic KDM8 variants that are resistant to hypoxic suppression reduces metastasis beyond that achieved by the wildtype Kdm8. Through the suppression of Kdm8 demethylase activity, hypoxia unleashes a potent metastatic program by simultaneously advancing cellular plasticity and chromosomal instability.
Published in
Hypoxia-induced metastatic heterogeneity in pancreatic cancer
Gunasekaran PM, Wang Q, Chang YC et al. · Research square 2025 · PMID 41255974 · doi:10.21203/rs.3.rs-7394295/v1
This dataset
Open GSE304599 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 GSE304599_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 PRJNA1301883 and SRA study SRP606609. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41255974) ↗
Study design
8 conditions, mostly in duplicate
Kdm8KO 688M PDA cells, Kdm8-WT, normoxia, clo… ×2 Kdm8KO 688M PDA cells, Kdm8-WT, hypoxia, clone ×2 Kdm8KO 688M PDA cells, Kdm8-H319A, normoxia, … ×2 Kdm8KO 688M PDA cells, Kdm8-H319A, hypoxia, c… ×2 Kdm8KO 688M PDA cells, Kdm8-W308Y, normoxia, … ×2 Kdm8KO 688M PDA cells, Kdm8-W308Y, hypoxia, c… ×2 Kdm8KO 688M PDA cells, Kdm8-W412N, normoxia, … ×2 Kdm8KO 688M PDA cells, Kdm8-W412N, hypoxia, c… ×2

Supports a between-group comparison across 16 samples.

How we read this: 8 replicated groups read from 16 sample titles; they account for 16 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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