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Targeting plasticity in the pyrimidine synthesis pathway potentiates macrophage-mediated phagocytosis in pancreatic cancer models

GSE262721 Mus musculus (mouse) RNA-seq (gene expression) 10 samples Submitted 2025/08/26 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 10 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
10 samples: 3 × Panc02 cell, untreat vs 3 × Panc02 cell, treated with TNFa vs 2 × Panc02 cell, sgCadGroups 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
Targeting plasticity in the pyrimidine synthesis pathway potentiates macrophage-mediated phagocytosis in pancreatic cancer modelsThe Journal of clinical investigation · 2025
Summary (written by the submitters)
Macrophage-mediated phagocytosis plays a pivotal role in eradicating cancer cells and modulating anti-tumor immunity. Yet, the mechanisms through which cancer cells evade phagocytosis remain elusive. We employed a genome-wide CRISPR screen in murine pancreatic cancer cells co-cultured with macrophages and discovered that disabling the tumor-intrinsic pyrimidine synthesis pathway (specifically Cad, Dhodh, and Umps) leads to enhanced phagocytosis by macrophages.
Read the full summary ↓
Mechanistically, macrophages suppress the UMP salvage pathway in tumor cells, increasing their dependence on de novo UMP synthesis. This suppression resulted in tumor cells with impaired de novo pyrimidine synthesis becoming more susceptible to apoptosis in the presence of macrophages, thereby enhancing macrophage-mediated elimination, both in vitro and in mouse models. Mechanistically, we show that pro-inflammatory cytokines released by macrophages, including TNFα and IL-1, are essential for upregulating Upp1 and decrease UMP pool in tumor cells. Thus, our findings uncover how tumor pyrimidine metabolism pathway shape their sensitivity to macrophage-mediated elimination.
Published in
Targeting plasticity in the pyrimidine synthesis pathway potentiates macrophage-mediated phagocytosis in pancreatic cancer models
Zhao J, Li X, Li X et al. · The Journal of clinical investigation 2025 · PMID 41243973 · doi:10.1172/JCI193370
This dataset
Open GSE262721 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 GSE262721_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 PRJNA1093055 and SRA study SRP498507. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41243973) ↗
Study design
3 × Panc02 cell, untreat vs 3 × Panc02 cell, treated with TNFa vs 2 × Panc02 cell, sgCad

Supports a between-group comparison across 8 samples.

How we read this: 3 replicated groups read from 10 sample titles; they account for 8 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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