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Myeloid-biased HSC require Semaphorin 4A from the bone marrow niche for self-renewal under stress and life-long persistence

GSE281145 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 10 samples Submitted 2024/12/11 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 10 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
10 samples: 4 × Sema4aKO_myHSC vs 4 × WT_myHSC vs 2 × WT_lyHSCGroups 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
Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cellsNature aging · 2025
Summary (written by the submitters)
Tissue stem cells are hierarchically organized. Those that are most primitive serve as key drivers of regenerative response but the signals that selectively preserve their functional integrity are largely unknown. Here, we identify a secreted factor, Semaphorin 4A (Sema4A), as a specific regulator of myeloid-biased hematopoietic stem cells (myHSC), which are positioned at the top of the HSC hierarchy.
Read the full summary ↓
Lack of Sema4A leads to exaggerated myHSC (but not downstream “balanced” HSC) proliferation after acute inflammatory stress, indicating that Sema4A enforces myHSC quiescence. Strikingly, aged Sema4A knock-out myHSC expand but almost completely lose reconstitution capacity. The effect of Sema4A is non cell-autonomous, since upon transplantation into Sema4A-deficient environment, wild-type myHSC excessively proliferate but fail to engraft long-term. Sema4A constrains inflammatory signaling in myHSC and acts via a surface receptor Plexin-D1. Our data support a model whereby the most primitive tissue stem cells critically rely on a dedicated signal from the niche for self-renewal and life-long persistence.
Published in
Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells
Toghani D, Gupte S, Zeng S et al. · Nature aging 2025 · PMID 39881190 · doi:10.1038/s43587-024-00798-7
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 GSE281145_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 peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1182374 and SRA study SRP543355. Searching any of these in the dataset finder brings you back here.

Study design
4 × Sema4aKO_myHSC vs 4 × WT_myHSC vs 2 × WT_lyHSC

Supports a between-group comparison across 10 samples.

How we read this: 3 replicated groups read from 10 sample titles; they account for 10 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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