GEO series

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 [scRNA-seq]

GSE276312 Mus musculus (mouse) Single-cell RNA-seq 23 samples Submitted 2025/02/12 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 23 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Mus musculus (mouse)
Samples: 23 samples: 9 conditions, mostly in duplicateGroups 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 GSE276312 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 GSE276312_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1156602 and SRA study SRP530456. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39803507) ↗

Study design

9 conditions, mostly in duplicate

GEX_Y665F_het_LN ×3 TCR_Y665F_het_LN ×3 GEX_WT_LN ×2 GEX_Y665F_homo_LN ×2 TCR_WT_LN ×2 TCR_Y665F_homo_LN ×2 GEX_WT_BM ×2 GEX_Y665H_BM ×2 +4 more

Supports a between-group comparison across 20 samples.

How we read this: 9 replicated groups read from 23 sample titles; they account for 20 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

GSM8496432 GEX_WT_LN-rep1 GEX_WT_LN
GSM8496433 GEX_WT_LN-rep2 GEX_WT_LN
GSM8496434 GEX_Y665F_het_LN-rep1 GEX_Y665F_het_LN
GSM8496435 GEX_Y665F_het_LN-rep2 GEX_Y665F_het_LN
GSM8496436 GEX_Y665F_het_LN-rep3 GEX_Y665F_het_LN
GSM8496437 GEX_Y665F_homo_LN-rep1 GEX_Y665F_homo_LN
GSM8496438 GEX_Y665F_homo_LN-rep2 GEX_Y665F_homo_LN
GSM8496439 TCR_WT_LN-rep1 TCR_WT_LN
GSM8496440 TCR_WT_LN-rep2 TCR_WT_LN
GSM8496441 TCR_Y665F_het_LN-rep1 TCR_Y665F_het_LN
GSM8496442 TCR_Y665F_het_LN-rep2 TCR_Y665F_het_LN
GSM8496443 TCR_Y665F_het_LN-rep3 TCR_Y665F_het_LN
GSM8496444 TCR_Y665F_homo_LN-rep1 TCR_Y665F_homo_LN
GSM8496445 TCR_Y665F_homo_LN-rep2 TCR_Y665F_homo_LN
GSM8496446 GEX_WT_Spleen-rep1
GSM8496447 GEX_Y665H_Spleen-rep1
GSM8496448 GEX_Y665F_Spleen-rep1
GSM8496449 GEX_WT_BM-rep1 GEX_WT_BM
GSM8496450 GEX_WT_BM-rep2 GEX_WT_BM
GSM8496451 GEX_Y665H_BM-rep1 GEX_Y665H_BM
GSM8496452 GEX_Y665H_BM-rep2 GEX_Y665H_BM
GSM8496453 GEX_Y665F_BM-rep1 GEX_Y665F_BM
GSM8496454 GEX_Y665F_BM-rep2 GEX_Y665F_BM

Datasets on a similar topic

GSE276311 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] 61 samples shares stat5b, sh2, hematopoiesis, controlling, mutations, leukemia, tyrosine
GSE276308 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 [ChIP-seq] 13 samples shares stat5b, sh2, hematopoiesis, controlling, mutations, leukemia, tyrosine
GSE270656 Human mutations, altering a single tyrosine in the STAT5B SH2 domain, have opposing impacts on enhancer function and mammary development [RNA-seq] 18 samples shares stat5b, sh2, mutations, tyrosine
GSE270652 Human mutations, altering a single tyrosine in the STAT5B SH2 domain, have opposing impacts on enhancer function and mammary development 65 samples shares stat5b, sh2, mutations, tyrosine
GSE310017 Disease-associated mutations on the STAT5B SH2 domain regulate cholesterol and lipid metabolism in liver [RNA-Seq liver] 37 samples shares stat5b, sh2, mutations
GSE310018 Disease-associated mutations on the STAT5B SH2 domain regulate cholesterol and lipid metabolism in liver 85 samples shares stat5b, sh2, mutations
GSE338662 STAT3 SH2 Domain Aspartic Acid 661 Mutations Activate Immune Gene Programs 18 samples shares sh2, mutations
GSE247343 Tyrosine phosphorylation of both STAT5A and STAT5B is necessary for maximal IL-2 signaling and its mitogenic action 57 samples shares stat5b, tyrosine

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