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In vivo single-cell CRISPR uncovers distinct TNF-α programs in tumor evolution

GSE235325 Mus musculus (mouse) Single-cell RNA-seq 256 samples Submitted 2024/07/17 Platform GPL34328Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 256 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
256 samples: 6 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
In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolutionNature · 2024
Summary (written by the submitters)
The tumor evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues1-3, the mechanisms behind why only a small number of clones transform into malignant tumors remain enigmatic.
Read the full summary ↓
Here, we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programs at single-cell transcriptomic resolution. We uncover a TNF-α signaling module, dependent on TNF receptor 1 and involving macrophages, that acts as a generalizable driver of clonal expansions in epithelial tissues. Conversely, during tumorigenesis, the TNF-α signaling module is downregulated. Instead, we identify a subpopulation of invasive cancer cells that switch to an autocrine TNF-α gene program, associated with epithelial-mesenchymal transition. Finally, we provide in vivo evidence that the autocrine TNF-α gene program is sufficient to mediate invasive properties and show that the TNF-α signature correlates with shorter overall survival in human squamous cell carcinoma patients. Collectively, our study demonstrates the power of applying in vivo single-cell CRISPR screening to mammalian tissues, unveils distinct TNF-α programs in tumor evolution and highlights the importance of understanding the relationship between clonal expansions in epithelia and tumorigenesis.
Published in
In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution
Renz PF, Ghoshdastider U, Baghai Sain S et al. · Nature 2024 · PMID 39020166 · doi:10.1038/s41586-024-07663-y
This dataset
Open GSE235325 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 GSE235325_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 PRJNA985698 and SRA study SRP445103. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39020166) ↗
Study design
6 conditions, mostly in duplicate
Amplicon sequencing of genomic DNA, DMBA/TPA-… ×168 Amplicon sequencing of genomic DNA, TNFR1ko P… ×4 in vitro keratinocytes, mCherry negative, ×2 in vitro keratinocytes, mCherry positive, ×2 in vitro keratinocytes, mCherry negative, ant… ×2 in vitro keratinocytes, mCherry positive, ant… ×2 Sample_4_WTA ×1 Sample_5_WTA ×1 +74 more

Supports a case/control comparison: 174 samples read as cases, 14 as controls.

How we read this: 6 replicated groups read from 256 sample titles; they account for 180 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

+ 216 more — browse all 256 samples with per-sample file links →

Datasets on a similar topic

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