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Genome-wide screen identifies Runx2 as a novel regulator of hematopoietic stem cell expansion and T-cell commitment

GSE288012 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 20 samples Submitted 2025/11/27 Platform GPL34328
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 20 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
20 samples: 6 conditions, mostly in triplicateGroups 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
A genome-wide screen identifies Runx2 as a novel regulator of hematopoietic stem cell expansion and T-cell commitmentBlood · 2025
Summary (written by the submitters)
Self-renewing multipotent hematopoietic stem cells (HSCs) are a rare but important cell population which can reconstitute the entire blood and immune system following transplantation. Due to their rarity, it has been difficult to comprehensively study the mechanisms regulating HSC activity. However, recent improvements in hematopoietic stem and progenitor cell (HSPC) culture methods using polyvinyl alcohol (PVA)-based media now facilitate large-scale ex vivo HSC expansion.
Read the full summary ↓
Here we performed a genome-wide CRISPR knockout (KO) screen in primary mouse HSPCs to discover novel regulators of ex vivo expansion. The screen identified Runx2 as a strong negative regulator of HSC expansion, which we validated using ex vivo and in vivo assays. Loss of Runx2 increased the frequency of immunophenotypic HSCs in HSPC cultures by ~3-fold. Following expansion, Runx2-KO HSCs engrafted at ~5-fold higher levels in competitive transplantation assays. Non-cultured Runx2-KO HSCs also displayed enhanced reconstitution potential, but loss of Runx2 did not alter blood parameters. Notably however, T-cell reconstitution was diminished from Runx2-KO HSCs, and we further validated an additional role for Runx2 in T-cell commitment using ex vivo and in vivo assays. In summary, we have identified a multifaceted role for Runx2 in HSCs, as a negative regulator of HSC self-renewal and as a facilitator of T-cell commitment. These results will contribute understanding transcriptional regulation of hematopoiesis and improve HSC therapies.
Published in
A genome-wide screen identifies Runx2 as a novel regulator of hematopoietic stem cell expansion and T-cell commitment
Meaker GA, Nicholls M, Chahrour C et al. · Blood 2025 · PMID 40961240 · doi:10.1182/blood.2025029115
This dataset
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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 GSE288012_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 PRJNA1215449 and SRA study SRP559754. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40961240) ↗
Study design
6 conditions, mostly in triplicate
CD201+CD150+KSL Runx2-heterozygous knockout c… ×3 CD201+CD150+KSL Runx2-homozygous knockout cul… ×3 CD201+CD150+KSL wild-type cultured HSC RNA-seq ×3 CD201-CD150-KSL Runx2-heterozygous knockout c… ×3 CD201-CD150-KSL Runx2-homozygous knockout cul… ×3 CD201-CD150-KSL wild-type cultured HPC RNA-seq ×3 CD201+CD150+KSL wild-type cultured HSC CUT&Ta… ×1 CD201+CD150+KSL wild-type cultured HSC CUT&Ta… ×1

Supports a case/control comparison: 12 samples read as cases, 8 as controls.

How we read this: 6 replicated groups read from 20 sample titles; they account for 18 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
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