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Cell of origin epigenetic priming determines susceptibility to Tet2 oncogenic mutation [scATAC-seq]

GSE227314 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 16 samples Submitted 2024/03/14 Platform GPL21626
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 16 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
16 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
Cell of origin epigenetic priming determines susceptibility to Tet2 mutationNature communications · 2024
Summary (written by the submitters)
Hematopoietic stem cell mutations can result in clonal hematopoiesis (CHIP) but the clinical outcomes are heterogeneous. The nature of the founder mutation and secondary mutations likely drive emergent neoplastic disease. We investigated how the cell state where the TET2 mutation occurs affects susceptibility to that commonly occurring CH mutation.
Read the full summary ↓
Here, we provide evidence that risk is written in the epigenome of the cell of origin. By characterizing cell states that underlie myeloid differentiation and linking this information to an inducible system to assess myeloid progenitor clones, we provide evidence that epigenetic markers of the cell where Tet2 mutation occurs stratifies clonal behaviors. Specifically, Sox4 fosters a global cell state of high sensitization towards Tet2 KO. Using GMP and primary HSC models, we show that Sox4 promotes cell dedifferentiation, alters cell metabolism and increases the in vivo clonal output of mutant cells. Our results validate the hypothesis that epigenetic features can predispose specific clones for dominance and explain why an identical mutation can result in different outcomes.
Published in
Cell of origin epigenetic priming determines susceptibility to Tet2 mutation
Schiroli G, Kartha V, Duarte FM et al. · Nature communications 2024 · PMID 38773071 · doi:10.1038/s41467-024-48508-6
This dataset
Open GSE227314 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE227314_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA944632 and SRA study SRP427252. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38773071) ↗
Study design
6 conditions, mostly in duplicate
GMP_Tet2 ×4 Lin_neg_CD11b_Tet2 ×4 GMP_Control ×2 Lin_neg_CD11b_Control ×2 GMP_Tet2_Sox4OE ×2 Lin_neg_CD11b_Tet2_Sox4OE ×2

Supports a between-group comparison across 16 samples.

How we read this: 6 replicated groups read from 16 sample titles; they account for 16 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
Datasets on a similar topic

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