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Two mutations associated with leukemia that change a single tyrosine residue in the STAT5B SH2 domain have opposite effects on the transcriptional programs controlling hematopoiesis [RNA-seq]

GSE276311 Mus musculus (mouse) RNA-seq (gene expression) 61 samples Submitted 2025/02/12 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 61 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
61 samples: 17 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
STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programsbioRxiv : the preprint server for biology · 2024
Summary (written by the submitters)
Normal hematopoiesis is regulated by various cytokines via the JAK-STAT signaling pathway. Gene deletion studies in mice have demonstrated the crucial role of STAT5B in the proliferation, differentiation, and survival of immune cells. However, the physiological effects of human STAT5B mutations remain poorly understood. Mutations within the SH2 domain of STAT5B have been identified in leukemia patients.
Read the full summary ↓
In this study, we investigate two specific variants: one that substitutes tyrosine 665 with phenylalanine (STAT5BY665F) and another that substitutes tyrosine 665 with histidine (STAT5BY665H). We introduced these two mutations into the mouse genome and observed distinct and divergent impacts on immune cell function. The STAT5BY665F mutation enhanced STAT5B activity and the establishment of transcriptional enhancers and genetic programs. Conversely, the STAT5BY665H mutation was largely inactive, failing to induce the interleukin-regulated enhancer landscape and gene expression. Both mutations modified immune cell profiles, inducing features characteristic of autoimmune disease. In STAT5BY665F mice, there was an expansion of CD8+ and regulatory CD4+ T cells, whereas STAT5BY665H mice didn’t. Both mutant strains exhibited skin abnormalities; however, only the STAT5BY665F mice developed progressive dermatitis. Introduction of equivalent mutations into STAT5A did not significantly impact hematopoiesis. However, mice carrying mutations in both STAT5A and STAT5B displayed additive effects with highly elevated CD4+ and CD8+ T cells. Our findings demonstrate that different naturally occurring missense mutations identified in leukemia patients, changing a single amino acid within the SH2 domain, can either activate or inactivate STAT5B and thereby impact T cell populations.
Published in
STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs
Lee HK, Chen J, Philips RL et al. · bioRxiv : the preprint server for biology 2024 · PMID 39803507 · doi:10.1101/2024.12.20.629685
This dataset
Open GSE276311 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 GSE276311_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 PRJNA1156603 and SRA study SRP530436. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39803507) ↗
Study design
17 conditions, mostly in triplicate
Y665F_Splenocyte ×7 Y665H_Splenocyte ×5 WT_T_IL ×4 Y665H_T_IL ×4 Y665F_T_IL ×4 WT_Splenocyte ×4 S5KO_CD4 ×3 S5KO_CD4_Stat5b ×3 +9 more

Supports a between-group comparison across 61 samples.

How we read this: 17 replicated groups read from 61 sample titles; they account for 61 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

+ 21 more — browse all 61 samples with per-sample file links →

Datasets on a similar topic

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