GEO series

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

GSE236726 Mus musculus (mouse) Single-cell RNA-seq 13 samples Submitted 2024/06/21 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 13 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: 13 samples: 13 samples, each with a distinct title — no replicated groupsGroups 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 GSE236726 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 GSE236726_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 PRJNA992210 and SRA study SRP447853. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

13 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 13 sample titles: 13 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

GSM7574572 B16_WT1 stranded RNA-Seq
GSM7574573 B16_WT2 stranded RNA-Seq
GSM7574574 B16_Trp53KO1 stranded RNA-Seq
GSM7574575 B16_Trp53KO2 stranded RNA-Seq
GSM7574576 B16_TdgKO1 stranded RNA-Seq
GSM7574577 B16_TdgKO2 stranded RNA-Seq
GSM7574578 B16_TdgTrp53_DKO1 stranded RNA-Seq
GSM7574579 B16_TdgTrp53_DKO2 stranded RNA-Seq
GSM7574580 KP_WT1 stranded RNA-Seq
GSM7574581 KP_WT2 stranded RNA-Seq
GSM7574582 KP_TdgKO1 stranded RNA-Seq
GSM7574583 KP_TdgKO2 stranded RNA-Seq
GSM7574584 KP_TdgKO3 stranded RNA-Seq

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, 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
GSE277171 A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance [RNA-seq] 70 samples shares essentiality, rna-seq
GSE272602 DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (RNA-Seq) 24 samples shares glycosylase, rna-seq
GSE269373 Engineering Programmable Material-To-Cell Pathways Via Synthetic Notch Receptors To Spatially Control Cellular Phenotypes In Multi-Cellular Constructs [RNA-seq] 22 samples shares synthetic, rna-seq
GSE287894 Biosynthetic plasticity enables CD8+ T cell functional resilience under nutrient stress [Atf4 & Cebpg KO RNA-seq] 18 samples shares synthetic, rna-seq

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