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Fibroblast-like cells in mesothelioma can derive from tumor cells

GSE253973 Homo sapiens (human) Single-cell RNA-seq 11 samples Submitted 2025/12/12 Platform GPL18573
At a glance

Single-cell RNA-seq · human · 11 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
Homo sapiens (human)
Topic
MesotheliomaThis series is part of our curated briefing on it.
Samples
11 samples: 5 × Mesothelioma tumor biposy MOS vs 3 × PDO from MOSGroups 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
Fibroblast-like cells in mesothelioma can derive from tumor cellsCell death and differentiation · 2026
Summary (written by the submitters)
Pleural mesothelioma (PM) is an aggressive cancer that originates from mesothelial cells lining the pleura. To identify the different cell types in mesothelioma and their relationships, we performed single-cell RNAseq analyses of non-malignant pleura biopsies, PM biopsies and PM patient-derived organoids. Gene expression profiles of mesothelial and mesothelioma cells are very similar, suggesting that mesothelioma cells retain most properties of mesothelial cells.
Read the full summary ↓
Surprisingly, in PM patient-derived organoids mesothelioma cells can acquire a fibroblast-like gene expression profile. Indeed, in most of the original PM biopsies a fraction of cells within the cluster of cancer-associated fibroblasts (CAFs) appear derived from tumor cells, with which they share the same genomic rearrangements. We confirmed by immunohistochemistry, and thus at the protein level, that cancer-derived fibroblast-like cells (CDFs) express smooth muscle actin, as most CAFs do, but have lost the same tumor suppressor proteins as the cognate mesothelioma cells. We propose that mesothelioma cells can become CDFs because they retain the ability of mesothelial cells to differentiate into fibroblasts. CDFs are thus tumor cells with fibroblast-like gene expression associated to tumors, and fulfil the definition of CAFs. CAFs generally support tumor progression, and in most tumors derive from resident fibroblasts or circulating mesenchymal cells. Our finding that a subset of CAFs derive from tumor cells, at least in mesothelioma, challenges current understanding of CAF origin. We suggest that interfering with the mesothelioma-to-CAF transition might offer an avenue to moderate tumor progression and resistance to therapy.
Published in
Fibroblast-like cells in mesothelioma can derive from tumor cells
Garcia-Manteiga JM, Rrapaj E, Caprioglio F et al. · Cell death and differentiation 2026 · PMID 41402607 · doi:10.1038/s41418-025-01639-9
This dataset
Open GSE253973 in finder → Find more human RNA-seq datasets → Mesothelioma landscape →
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 GSE253973_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 PRJNA1068028 and SRA study SRP485403. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41402607) ↗
Study design
5 × Mesothelioma tumor biposy MOS vs 3 × PDO from MOS

Supports a between-group comparison across 8 samples.

How we read this: 2 replicated groups read from 11 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
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