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Dnmt3a Controls Hematopoietic Stem Cells via DNA Methylation-Independent Regulation of Telomeres

GSE272913 Mus musculus (mouse) DNA methylation 66 samples Submitted 2024/09/10 Platform GPL34290Platform GPL24247
At a glance

DNA methylation · mouse · 66 samples

What it is
DNA methylationChemical marks on DNA that help switch genes on or off.
Organism
Mus musculus (mouse)
Samples
66 samples: 66 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.
Paper
Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrityCell stem cell · 2025
Summary (written by the submitters)
Dnmt3a is the most recurrently mutated gene in clonal hematopoiesis (CH) and it is a critical regulator of hematopoietic stem cells (HSCs). Conditional deletion of Dnmt3a in mouse HSC results in enhanced self-renewal but impaired differnetiation. Dnmt3a encodes for a de novo DNA methyltransferase enzyme but both mouse and human cells with loss of Dnmt3a show minimal change in DNA methylation levels which do not correlate with gene expression differences.
Read the full summary ↓
To understand if these changes are due to non-canonical function of Dnmt3a, we generated varying levels of DNA methyaltion-impared Dnmt3a mouse models. Our data depicts that DNA methyaltion-impaired Dnmt3a phenocopy wild-type in serial transplant. And Dnmt3a methyltransferase-deficient HSCs showed differntially methylated regions (DMRs) and gene expression pattern that overlapped with Dnmt3a-null HScs. Suggesting that Dnmt3a has important non-canonical function that partially regulates HSC fate. Dnmt3a-null HSC increased HSC self-renwal and can be transplanted indefinitely and increase longevity with no erosion of telomere length. Dnmt3a-null HSCs showed increased telomere at baseline and maintained overa serial transplant and increased telomerase activity. The role of Dnmt3a in telomere maintenance was not strictly linked to elongated telomere length but in regulation of DNA damage response that occurs at stressed telomeres. These data show a unidentified role of Dnmt3a in HSC telomere maintenance that is note related to DNA methylation function.
Published in
Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrity
Xavier Raj I, Kyun Koh W, Harrison J et al. · Cell stem cell 2025 · PMID 40680747 · doi:10.1016/j.stem.2025.06.010
This dataset
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.

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 GSE272913_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1139218 and SRA study SRP521804. Searching any of these in the dataset finder brings you back here.

Study design
66 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 66 sample titles: 66 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

+ 26 more — browse all 66 samples with per-sample file links →

Datasets on a similar topic

Search all mouse methylation 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.