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Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells [bulk ATAC-seq]

GSE233986 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 14 samples Submitted 2025/08/29 Platform GPL21626Platform GPL13112
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 14 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
14 samples: 5 × ATAC-Seq - HSC - aged control vs 5 × ATAC-Seq - HSC - aged + RhoA-inhibitor (Ri) vs 4 × ATAC-Seq - HSC - young controlGroups 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
Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cellsNature aging · 2026
Summary (written by the submitters)
Biomechanical alterations contribute to the decreased regenerative capacity of hematopoietic stem cells (HSCs) upon aging. RhoA is a key regulator o­f m­ec­ha­no­si­gn­aling, but its role i­n m­ec­ha­no­tr­an­sd­uction in stem cell aging remains unclear. Here we show that murine HSCs respond to increased nuclear envelope (NE) tension by inducing NE translocation of P-cPLA2, which cell-intrinsically activates RhoA.
Read the full summary ↓
Aged HSCs experience physiologically higher intrinsic NE tension, but reducing RhoA activity lowers NE tension in aged HSCs. Feature image analysis of HSC nuclei reveals that chromatin remodeling is associated with RhoA inhibition, including restoration of youthful levels of t­he h­et­er­oc­hr­omatin m­ar­ker H3K9me2 and a decrease in chromatin accessibility and transcription at retrotransposons. Finally, we demonstrate that RhoA inhibition upregulates Klf4 expression and transcriptional activity, improving aged HSC regenerative capacity and lympho/myeloid skewing in vivo. Together, our data outline an intrinsic RhoA-dependent mechanosignaling axis, which can be pharmacologically targeted to restore aged stem cell function.
Published in
Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells
Mejía-Ramírez E, Picazo PI, Walter B et al. · Nature aging 2026 · PMID 41286464 · doi:10.1038/s43587-025-01014-w
This dataset
Open GSE233986 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 GSE233986_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 PRJNA979159 and SRA study SRP440946. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41286464) ↗
Study design
5 × ATAC-Seq - HSC - aged control vs 5 × ATAC-Seq - HSC - aged + RhoA-inhibitor (Ri) vs 4 × ATAC-Seq - HSC - young control

Supports a between-group comparison across 14 samples.

How we read this: 3 replicated groups read from 14 sample titles; they account for 14 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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