GEO series

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

GSE236720 Mus musculus (mouse) Single-cell RNA-seq 26 samples Submitted 2024/06/21 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 26 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: 26 samples: 24 distinct titles, 2 of them repeatedGroups 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)

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

Open GSE236720 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 GSE236720_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 PRJNA992087 and SRA study SRP447776. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

24 distinct titles, 2 of them repeated

KP_DMSO ×2 KP_C271 ×2

How we read this: Read from 26 sample titles: 24 distinct titles with little repetition. 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

GSM7574442 KP_WT1 RNA-Seq
GSM7574443 KP_WT2 RNA-Seq
GSM7574444 KP_WT3 RNA-Seq
GSM7574445 KP_TdgKO1 RNA-Seq
GSM7574446 KP_TdgKO2 RNA-Seq
GSM7574447 KP_TdgKO3 RNA-Seq
GSM7574448 KP1 RNA-Seq
GSM7574449 KP2 RNA-Seq
GSM7574450 KPT1 RNA-Seq
GSM7574451 KPT2 RNA-Seq
GSM7574452 KPT3 RNA-Seq
GSM7574453 KPT4 RNA-Seq
GSM7574454 B16_WT1 RNA-Seq
GSM7574455 B16_WT2 RNA-Seq
GSM7574456 B16_TdgKO1 RNA-Seq
GSM7574457 B16_TdgKO2 RNA-Seq
GSM7574458 B16_Trp53KO1 RNA-Seq
GSM7574459 B16_Trp53KO2 RNA-Seq
GSM7574460 B16_TdgTrp53_DKO1 RNA-Seq
GSM7574461 B16_TdgTrp53_DKO2 RNA-Seq
GSM7574462 B16_TdgTrp53Mavs_TKO1 RNA-Seq
GSM7574463 B16_TdgTrp53Mavs_TKO2 RNA-Seq
GSM8816211 KP_DMSO_1
GSM8816212 KP_DMSO_2
GSM8816213 KP_C271_1
GSM8816214 KP_C271_2

Datasets on a similar topic

GSE236726 Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [strand specific RNA-seq] 13 samples shares p53-deficient, essentiality, glycosylase, synthetic, thymine, rna-seq
GSE236727 Synthetic essentiality of thymine DNA glycosylase in p53-deficient cancer [scRNA-seq] 2 samples shares p53-deficient, essentiality, glycosylase, synthetic, thymine, rna-seq
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
GSE254388 CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality [RNA-Seq] 14 samples shares synthetic, rna-seq
GSE266951 Increased translation driven by a non-canonical EZH2 cistrome creates a synthetic vulnerability in enzalutamide-resistant prostate cancer (RNA-Seq organoids) 6 samples shares synthetic, rna-seq
GSE254387 CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality [scRNA-Seq] 6 samples shares synthetic, rna-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, rna-seq

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