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Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer [RNA-seq]

GSE291118 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2025/05/16 Platform GPL34475
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 5 × Murine CAFs treated with 0.2 mM glutamine + 25 uM EIPA, vs 5 × Murine CAFs treated with 0.2 mM glutamine + DMSO, vs 5 × Murine CAFs treated with 4 mM glutamine + DMSO + 25 pg/mL IL1a, vs 5 × Murine CAFs treated with 4 mM glutamine + DMSO,Groups 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
Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancerCancer cell · 2025
Summary (written by the submitters)
Pancreatic ductal adenocarcinoma (PDAC) tumors are deficient in glutamine, an amino acid that tumor cells and cancer-associated fibroblasts (CAFs) use to sustain their fitness. In PDAC, both cell types stimulate macropinocytosis as an adaptive response to glutamine depletion. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive.
Read the full summary ↓
In this study, we find that macropinocytosis functions to control CAF subtype identity when glutamine is limiting. Our data demonstrate that metabolic stress leads to an intrinsic inflammatory CAF (iCAF) program driven by MEK/ERK signaling. Utilizing in vivo models, we find that blocking macropinocytosis triggers CAF subtype transitions and reorganizes the tumor stroma. Importantly, these changes in stromal architecture can be exploited to sensitize PDAC to immunotherapy and chemotherapy. Our findings demonstrate that metabolic stress plays a role in shaping the tumor microenvironment, and that this attribute can be harnessed for therapeutic impact.
Published in
Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer
Zhang Y, Ling L, Murad R et al. · Cancer cell 2025 · PMID 40712568 · doi:10.1016/j.ccell.2025.06.021
This dataset
Open GSE291118 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 GSE291118_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 PRJNA1232029 and SRA study SRP568043. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40712568) ↗
Study design
5 × Murine CAFs treated with 0.2 mM glutamine + 25 uM EIPA, vs 5 × Murine CAFs treated with 0.2 mM glutamine + DMSO, vs 5 × Murine CAFs treated with 4 mM glutamine + DMSO + 25 pg/mL IL1a, vs 5 × Murine CAFs treated with 4 mM glutamine + DMSO,

Supports a between-group comparison across 20 samples.

How we read this: 4 replicated groups read from 20 sample titles; they account for 20 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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