GEO series

Maintenance of ESLAM haematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition

GSE223366 Mus musculus (mouse) RNA-seq (gene expression) 288 samples Submitted 2024/05/29 Platform GPL17021

At a glance

RNA-seq (gene expression) · mouse · 288 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: 288 samples
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: Maintenance of hematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibitionBlood advances · 2025

Summary (written by the submitters)

Adult haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells and must respond to extracellular cues including cytokines. The JAK/STAT pathway is a highly conserved pathway, activated by many cytokines, in which tyrosine-phosphorylated STATs (pSTATs) function as transcription factors. STAT5 is a pivotal downstream mediator of several cytokines known to regulate haematopoiesis but its function in the HSC compartment remains poorly understood.

Read the full summary ↓

Here we show that STAT5-deficient HSCs exhibited an unusual phenotype - reduced multi-lineage repopulation and self-renewal combined with reduced cell cycle entry and increased differentiation. This reflected not only loss of a canonical pSTAT5 transcriptional program but also loss of distinct functions mediated by tyrosine-unphosphorylated STAT5 (uSTAT5). Consistent with this concept expression of an unphosphorylatable STAT5B mutant constrained HSC differentiation, promoted HSC maintenance and upregulated transcriptional programs associated with quiescence and stemness. Moreover, treatment with a JAK1/2 inhibitor (ruxolitinib) increased the uSTAT5:pSTAT5 ratio, constrained HSC differentiation and proliferation and promoted HSC maintenance, thus phenocopying uSTAT5B overexpression. Our results therefore reveal a previously unrecognized interplay between pSTAT5 and uSTAT5 in the control of HSC function. In addition the demonstration that JAK inhibition promotes HSC maintenance has implications for gene therapy using HSCs and may contribute to the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.

Published in

Maintenance of hematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition

Williams MJ, Wang X, Bastos HP et al. · Blood advances 2025 · PMID 39374575 · doi:10.1182/bloodadvances.2024014046

This dataset

Open GSE223366 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 GSE223366_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 PRJNA925879 and SRA study SRP418456. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39374575) ↗

Samples in this study

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+ 288 more — browse all 288 samples with per-sample file links →

Datasets on a similar topic

GSE223632 Maintenance of haematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition - STAT5 deficient HSPCs (LK) 6 samples shares stat5, jak, tyrosine-unphosphorylated, haematopoietic, maintenance, inhibition, stem
GSE278496 HiJAKing the hematopoietic system: a low-frequency JAK2V617F clone drives myeloproliferative neoplasm pathology 43 samples shares jak, stem
GSE272694 Crnic Institute - Trisomy 21 Model Atlas: PolyA RNA-seq from 6-month old mouse brain hippocampus tissue ± JAK1/3 inhibition with tofacitinib 34 samples shares jak, inhibition
GSE272693 Crnic Institute - Trisomy 21 Model Atlas: PolyA RNA-seq from 6-month old mouse brain cortex tissue ± JAK1/3 inhibition with tofacitinib 34 samples shares jak, inhibition
GSE230771 Differential Effects of JAK1 vs. JAK2 Inhibition in Mouse Models of Hemophagocytic Lymphohistiocytosis 30 samples shares jak, inhibition
GSE268268 JAK/STAT inhibition restores disease tolerance in malaria-infected glucocorticoid receptor knockout mice. 18 samples shares jak, inhibition
GSE335822 In vitro inhibition of STAT5 signaling limits CD8⁺ T-cell exhaustion and improves outcomes in adoptive T-cell therapy models. 15 samples shares stat5, inhibition
GSE249303 The effects of JAK inhibition on SARS-CoV-2-induced kidney injury 9 samples shares jak, inhibition

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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.