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Twist1 Overexpression Models an Aggressive Subtype of Pancreatic Ductal Adenocarcinoma in vivo

GSE291909 Mus musculus (mouse) Single-cell RNA-seq 25 samples Submitted 2026/06/30 Platform GPL34290
At a glance

Single-cell RNA-seq · mouse · 25 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
25 samples: 5 conditions, mostly in triplicateGroups 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.
Summary (written by the submitters)
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with very poor survival outcomes. Genomic analyses have identified distinct molecular subtypes in human PDAC with quasimesenchymal/squamous/basal-like (QSB) having the worse prognosis. However, no in vivo models exist for QSB subtypes. The epithelial-mesenchymal transition (EMT) transcription factor TWIST1 is upregulated in QSB PDAC.
Read the full summary ↓
We hypothesized that the TWIST1-dependent plasticity program is a key regulator of QSB PDAC subtype development. Non-negative matrix factorization (NMF) of human PDAC subtypes identified 3 NMF clusters. NMF1 was dominated by QSB subtypes, had the worst overall survival, and exhibited high TWIST1 expression. We generated a novel tetracycline-inducible autochthonous pancreas specific KrasG12D-Twist1 genetically engineered tumor mouse model (Pdx1 promoter-Cre (P); LSL-KrasG12D (R); LSL-rtTA-IRES-GFP (G); Twist1-tetO-Luc (T)). PGRT mice showed accelerated pancreatic tumor development and decreased overall median survival compared to PGR (KrasG12D alone) mice (4.6 months vs 9.7 months, p< 0.0001). Histological analyses showed that PGRT pancreatic tumors spanned a spectrum of PDAC to QSB PDAC subtype, exhibited an EMT profile and squamous histology. Twist1 induction resulted in increased metastases (9.52 % PGR at 48 weeks vs 73.91% PGRT at 24 weeks, p<0.0001). PGRT tumors demonstrated gene expression programs related to collagen content, EMT and cell movement and was most concordant with human QSB PDAC subtypes and squamoid single cell subtype. Twist1 overexpression cooperated with KrasG12D for PDAC development in vivo and progression towards metastasis and mimicked the human QSB PDAC subtypes. This novel model may offer new perspectives for PDAC research and for the testing of novel therapeutic strategies in an aggressive PDAC subtype.
This dataset
Open GSE291909 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 GSE291909_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1235761 and SRA study SRP570342. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 conditions, mostly in triplicate
KrasG12D+Twist1 overexpression Late, ×9 KrasG12D+Trp53R172H, ×6 Twist1 Overexpression, ×4 KrasG12D, ×3 KrasG12D+Twist1 overexpression Early, ×3

Supports a between-group comparison across 25 samples.

How we read this: 5 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
Datasets on a similar topic

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