GEO series

Human mutations, altering a single tyrosine in the STAT5B SH2 domain, have opposing impacts on enhancer function and mammary development [RNA-seq]

GSE270656 Mus musculus (mouse) Single-nucleus RNA-seq 18 samples Submitted 2025/04/09 Platform GPL24247Platform GPL21493

At a glance

Single-nucleus RNA-seq · mouse · 18 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 18 samples: 5 conditions, mostly with about 4 replicates eachGroups 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: Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary DevelopmentJournal of mammary gland biology and neoplasia · 2025

Summary (written by the submitters)

Mammary gland development during pregnancy is controlled by lactogenic hormones via the JAK2-STAT5 pathway. Gene deletion studies in mice have revealed the crucial roles of both STAT5A and STAT5B in establishing the genetic programs necessary for the development of mammary epithelium and successful lactation. Several hundred single nucleotide polymorphisms (SNPs) have been identified in human STAT5B, although their pathophysiological significance remains largely unknown.

Read the full summary ↓

The SH2 domain is vital for STAT5B activation, and this study focuses on the impact of two specific missense mutations identified in T cell leukemias, the substitution of tyrosine 665 with either phenylalanine (Y665F) or histidine (Y665H). By introducing these human mutations into the mouse genome, we uncovered distinct and opposite functions. Mice harboring the STAT5BY665H mutation failed to develop functional mammary tissue, resulting in lactation failure, while STAT5BY665F mice exhibited accelerated mammary development during pregnancy. Transcriptomic and epigenomic analyses identified STAT5BY665H as Loss-Of-Function (LOF) mutation, impairing enhancer establishment and alveolar differentiation, whereas STAT5BY665F acted as a Gain-Of-Function (GOF) mutation, elevating enhancer formation. Persistent hormonal stimulation through two pregnancies led to the establishment of enhancer structures, gene expression and successful lactation in STAT5BY665H mice. Lastly, we demonstrate that Olah, a gene known to drive life-threatening viral disease in humans, is regulated by STAT5B through a candidate four-partite super-enhancer. In conclusion, our findings underscore the role of human STAT5B variants in modulating mammary gland homeostasis and their critical impact on lactation.

Published in

Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development

Lee HK, Jankowski J, Liu C et al. · Journal of mammary gland biology and neoplasia 2025 · PMID 40163145 · doi:10.1007/s10911-025-09582-8

This dataset

Open GSE270656 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 GSE270656_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 PRJNA1127631 and SRA study SRP515854. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40163145) ↗

Study design

5 conditions, mostly with about 4 replicates each

STAT5B-Y665F-p13 ×4 STAT5B-Y665F-p18 ×4 STAT5B-Y665H-L10 ×4 WT-p13 ×3 STAT5B-Y665H-p18 ×3

Supports a between-group comparison across 18 samples.

How we read this: 5 replicated groups read from 18 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

GSM8349452 WT-p13_rep1 WT-p13
GSM8349453 WT-p13_rep2 WT-p13
GSM8349454 WT-p13_rep3 WT-p13
GSM8349455 STAT5B-Y665F-p13_rep1 STAT5B-Y665F-p13
GSM8349456 STAT5B-Y665F-p13_rep2 STAT5B-Y665F-p13
GSM8349457 STAT5B-Y665F-p13_rep3 STAT5B-Y665F-p13
GSM8349458 STAT5B-Y665F-p13_rep4 STAT5B-Y665F-p13
GSM8349459 STAT5B-Y665F-p18_rep1 STAT5B-Y665F-p18
GSM8349460 STAT5B-Y665F-p18_rep2 STAT5B-Y665F-p18
GSM8349461 STAT5B-Y665F-p18_rep3 STAT5B-Y665F-p18
GSM8349462 STAT5B-Y665F-p18_rep4 STAT5B-Y665F-p18
GSM8349463 STAT5B-Y665H-p18_rep1 STAT5B-Y665H-p18
GSM8349464 STAT5B-Y665H-p18_rep2 STAT5B-Y665H-p18
GSM8349465 STAT5B-Y665H-p18_rep3 STAT5B-Y665H-p18
GSM8493775 STAT5B-Y665H-L10_rep1 STAT5B-Y665H-L10
GSM8493776 STAT5B-Y665H-L10_rep2 STAT5B-Y665H-L10
GSM8493777 STAT5B-Y665H-L10_rep3 STAT5B-Y665H-L10
GSM8493778 STAT5B-Y665H-L10_rep4 STAT5B-Y665H-L10

Datasets on a similar topic

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, altering, tyrosine, opposing, enhancer, impacts
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, mutations, tyrosine
GSE276312 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] 23 samples shares stat5b, sh2, mutations, 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, 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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