GEO series

Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [scRNA-seq]

GSE236727 Mus musculus (mouse) Single-cell RNA-seq 2 samples Submitted 2024/06/21 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 2 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: 2 samples
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)

Thymine DNA Glycosylase (TDG) is a versatile protein involved in DNA mismatch repair, DNA demethylation, and transcriptional regulation. Here, we identify TDG as a synthetic essential effector in p53-deficient tumours. We found that deletion of TDG inhibits cell proliferation specifically in p53-deficient cancer cells. Using a genetically engineered mouse model of lung adenocarcinoma (LUAD), we demonstrate that depletion of TDG suppresses tumour growth in the p53-deficient context.

Read the full summary ↓

Notably, A novel and selective inhibitor developed to disrupt the DNA binding activity of TDG exhibits therapeutic efficacy against p53-deficient tumours in both cellular and xenograft models. Mechanistically, TDG coordinates with p53 to orchestrate the transcription of RNA helicase DHX9, which functions to eliminate dsRNA. Depletion of TDG in p53-deficient cells results in the downregulation of DHX9 and aberrant cytoplasmic double-strand (dsRNA) accumulation derived from Alu elements, subsequently activating the RIG-I/MDA5-MAVS mediated antiviral response. Moreover, single-cell RNA-sequencing analysis revealed the depletion of TDG in p53-deficient tumours facilitates the recruitment of tumour-infiltrating lymphocytes. We observed that TDG inhibition combined with immune checkpoint blockade (ICB) achieved a strong synergistic anti-tumour effect in p53-deficient tumours. This study highlights the function of TDG in maintaining p53-deficient tumour growth and provides an alternative therapeutic target for p53-deficient cancers.

This dataset

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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 GSE236727_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 PRJNA992209 and SRA study SRP447862. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 2 more — browse all 2 samples with per-sample file links →

Datasets on a similar topic

GSE236720 Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [RNA-seq] 26 samples shares p53-deficient, essentiality, glycosylase, synthetic, thymine
GSE236726 Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [strand specific RNA-seq] 13 samples shares p53-deficient, essentiality, glycosylase, synthetic, thymine
GSE236718 Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [CUT&Tag] 6 samples shares p53-deficient, essentiality, glycosylase, synthetic, thymine
GSE236717 Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [ATAC-seq] 5 samples shares p53-deficient, essentiality, glycosylase, synthetic, thymine
GSE254387 CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality [scRNA-Seq] 6 samples shares synthetic, scrna-seq
GSE266955 Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (scRNA-Seq) 4 samples shares synthetic, scrna-seq
GSE208680 Ex Utero Development of Post-Gastrulation Synthetic-Embryos Generated Solely from Mouse Naïve Pluripotent Stem Cells [scRNA-seq] 11 samples shares synthetic, scrna-seq
GSE259242 DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase 6 samples shares glycosylase, thymine

Search all mouse RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.