GEO series

Asxl1 mutation enhances differentiation in CSF3R-mutated myeloproliferative neoplasms [RNA-Seq]

GSE266091 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/01/22 Platform GPL23479

At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 12 samples: 3 × Empty/Empty vs 3 × Empty/T618I vs 3 × Asxl1-MT2/Empty vs 3 × Asxl1-MT2/T618IGroups 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: Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiationBlood advances · 2025

Summary (written by the submitters)

Mutations in the epigenetic regulator Additional Sex Combs-Like 1 (ASXL1) are frequently observed in chronic neutrophilic leukemia (CNL). This disease is classically driven by activating mutations in Colony Stimulating Factor 3 Receptor (CSF3R), which promote the overproduction of neutrophils that characterizes this disease. Despite high rates of co-occurrence, the interplay between ASXL1 and CSF3R mutations in hematopoiesis and leukemia development remains poorly understood.

Read the full summary ↓

Here, we present a new mouse model with both Asxl1Y588X and Csf3rT621I mutations, which recapitulates features of human CNL. Csf3r-mutant mice exhibit an age-associated depletion of hematopoietic stem and progenitor cells, which is reversed by the addition of Asxl1Y588X. This combination of mutations causes an expansion of myeloid-biased stem cells. As the mice age they develop neutrophilia, but leukemia is rare, suggesting additional mutations may be required for transformation. Using models of myeloid differentiation, we find that ASXL1 truncation enhances CSF3RT618I-driven neutrophil differentiation by downregulating MYC programs and activating inflammatory pathways associated with mature myeloid cell production. Moreover, cells with both mutations had increased priming of neutrophil-associated enhancers and reduced priming of enhancers associated with monocytic differentiation. Mutant ASXL1 is known to decrease genome-wide abundance of a repressive histone mark—H2AK119ub. While we see the expected decrease in H2AK119ub in Asxl1-mutant cells, this effect is reversed when CSF3R is also mutated, suggesting a complex interplay between these mutations in regulating chromatin dynamics during hematopoiesis. Our findings highlight context-dependent effects of ASXL1 mutation in myeloid disorders and provide insights into the mechanisms underlying neutrophil differentiation in ASXL1-mutant CNL.

Published in

Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiation

Darmusey L, Bagley AJ, Nguyen TT et al. · Blood advances 2025 · PMID 39777477 · doi:10.1182/bloodadvances.2024014362

This dataset

Open GSE266091 in finder → Find more mouse RNA-seq 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 GSE266091_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1105863 and SRA study SRP504588. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39777477) ↗

Study design

3 × Empty/Empty vs 3 × Empty/T618I vs 3 × Asxl1-MT2/Empty vs 3 × Asxl1-MT2/T618I

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM8240371 Empty/Empty_1 Empty/Empty
GSM8240372 Empty/Empty_2 Empty/Empty
GSM8240373 Empty/Empty_3 Empty/Empty
GSM8240374 Empty/T618I_1 Empty/T618I
GSM8240375 Empty/T618I_2 Empty/T618I
GSM8240376 Empty/T618I_3 Empty/T618I
GSM8240377 Asxl1-MT2/Empty_1 Asxl1-MT2/Empty
GSM8240378 Asxl1-MT2/Empty_2 Asxl1-MT2/Empty
GSM8240379 Asxl1-MT2/Empty_3 Asxl1-MT2/Empty
GSM8240380 Asxl1-MT2/T618I_1 Asxl1-MT2/T618I
GSM8240381 Asxl1-MT2/T618I_2 Asxl1-MT2/T618I
GSM8240382 Asxl1-MT2/T618I_3 Asxl1-MT2/T618I

Datasets on a similar topic

GSE266090 Asxl1 mutation enhances differentiation in CSF3R-mutated myeloproliferative neoplasms [Cut & Tag] 32 samples shares asxl1, myeloproliferative, csf3r-mutated, neoplasms, mutation, enhances
GSE266087 Asxl1 mutation enhances differentiation in CSF3R-mutated myeloproliferative neoplasms [ATAC-Seq] 12 samples shares asxl1, myeloproliferative, csf3r-mutated, neoplasms, mutation, enhances
GSE266848 Decoding Endothelial MPL and JAK2V617F Mutation: Insight into Cardiovascular Dysfunction in Myeloproliferative Neoplasms 2 samples shares myeloproliferative, neoplasms, mutation
GSE276811 Fructose feeding on Asxl1-mutant clonal hematopoiesis [single-cell RNA-seq] 12 samples shares asxl1, rna-seq
GSE208054 Inhibition of lysine demethylase 6B blocks the development of ASXL1 truncation-mediated myeloid malignancies [RNA-seq] 12 samples shares asxl1, rna-seq
GSE279601 Clonal Haematopoiesis-related Mutant ASXL1 Promotes Atherosclerosis in Mice via Dysregulated Innate Immunity [scRNA-seq] 4 samples shares asxl1, rna-seq
GSE269568 JAK2V617F Impairs Lymphoid Differentiation in Myeloproliferative Neoplasms 5 samples shares myeloproliferative, neoplasms
GSE228995 Cross-Talk between Haematopoietic Cells and Stromal cells Subsets Drives the Remodelling of the Bone Marrow Microenvironment in Myeloproliferative Neoplasms 22 samples shares myeloproliferative, neoplasms

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