GEO series

Disease-associated mutations on the STAT5B SH2 domain regulate cholesterol and lipid metabolism in liver [RNA-Seq liver]

GSE310017 Mus musculus (mouse) RNA-seq (gene expression) 37 samples Submitted 2026/02/12 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 37 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: 37 samples: 6 conditions, mostly with about 6 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 in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolismbioRxiv : the preprint server for biology · 2025

Summary (written by the submitters)

Growth hormone (GH) signaling through STAT5B is a central regulator of hepatic metabolism, yet the functional consequences of disease-associated STAT5B variants remain poorly understood. Here, we generated mice carrying STAT5BY665F (gain-of-function) and STAT5BY665H (loss-of-function) alleles using CRISPR/Cas9-mediated base editing to dissect their impact on metabolic regulation.

Read the full summary ↓

STAT5BY665F mutants developed hepatic lipid accumulation, hypercholesterolemia, and enhanced insulin sensitivity, whereas STAT5BY665H mice displayed reduced body weight and impaired insulin responsiveness. Transcriptomic analyses revealed that STAT5BY665F strongly activated lipid, cholesterol, and immune transcriptional programs, while STAT5BY665H failed to induce these pathways. ChIP-seq demonstrated extensive STAT5BY665F enhancer occupancy at metabolic and immune loci, contrasting with the minimal chromatin engagement of STAT5BY665H. Beyond the liver, STAT5BY665F broadly reprogrammed adipose tissue gene expression, activating lipid metabolism and immune regulatory networks, whereas STAT5BY665H exerted more restricted effects. Notably, transcriptional and chromatin remodeling by STAT5B variants displayed sex-dependent differences, with male livers showing more pronounced reprogramming than females. Together, these findings illustrate how alterations in STAT5B activity that alter enhancer activation led to altered metabolic function in liver and adipose tissue.

Published in

Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism

Lee HK, Pyatkov M, Gavrilova O et al. · bioRxiv : the preprint server for biology 2025 · PMID 41383779 · doi:10.1101/2025.11.27.691004

This dataset

Open GSE310017 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 GSE310017_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 PRJNA1365013 and SRA study SRP644988. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41383779) ↗

Study design

6 conditions, mostly with about 6 replicates each

Liver, Y665F_male ×9 Liver, WT_male ×6 Liver, WT_female ×6 Liver, Y665F_female ×6 Liver, Y665H_female ×6 Liver, Y665H_male ×4

Supports a between-group comparison across 37 samples.

How we read this: 6 replicated groups read from 37 sample titles; they account for 37 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

GSM9286518 Liver, WT_male_rep1 Liver, WT_male
GSM9286519 Liver, WT_male_rep2 Liver, WT_male
GSM9286520 Liver, WT_male_rep3 Liver, WT_male
GSM9286521 Liver, WT_male_rep4 Liver, WT_male
GSM9286522 Liver, WT_male_rep5 Liver, WT_male
GSM9286523 Liver, WT_male_rep6 Liver, WT_male
GSM9286524 Liver, Y665F_male_rep1 Liver, Y665F_male
GSM9286525 Liver, Y665F_male_rep2 Liver, Y665F_male
GSM9286526 Liver, Y665F_male_rep3 Liver, Y665F_male
GSM9286527 Liver, Y665F_male_rep4 Liver, Y665F_male
GSM9286528 Liver, Y665F_male_rep5 Liver, Y665F_male
GSM9286529 Liver, Y665F_male_rep6 Liver, Y665F_male
GSM9286530 Liver, Y665F_male_rep7 Liver, Y665F_male
GSM9286531 Liver, Y665F_male_rep8 Liver, Y665F_male
GSM9286532 Liver, Y665F_male_rep9 Liver, Y665F_male
GSM9286533 Liver, Y665H_male_rep1 Liver, Y665H_male
GSM9286534 Liver, Y665H_male_rep2 Liver, Y665H_male
GSM9286535 Liver, Y665H_male_rep3 Liver, Y665H_male
GSM9286536 Liver, Y665H_male_rep4 Liver, Y665H_male
GSM9286537 Liver, WT_female_rep1 Liver, WT_female
GSM9286538 Liver, WT_female_rep2 Liver, WT_female
GSM9286539 Liver, WT_female_rep3 Liver, WT_female
GSM9286540 Liver, WT_female_rep4 Liver, WT_female
GSM9286541 Liver, WT_female_rep5 Liver, WT_female
GSM9286542 Liver, WT_female_rep6 Liver, WT_female
GSM9286543 Liver, Y665F_female_rep1 Liver, Y665F_female
GSM9286544 Liver, Y665F_female_rep2 Liver, Y665F_female
GSM9286545 Liver, Y665F_female_rep3 Liver, Y665F_female
GSM9286546 Liver, Y665F_female_rep4 Liver, Y665F_female
GSM9286547 Liver, Y665F_female_rep5 Liver, Y665F_female
GSM9286548 Liver, Y665F_female_rep6 Liver, Y665F_female
GSM9286549 Liver, Y665H_female_rep1 Liver, Y665H_female
GSM9286550 Liver, Y665H_female_rep2 Liver, Y665H_female
GSM9286551 Liver, Y665H_female_rep3 Liver, Y665H_female
GSM9286552 Liver, Y665H_female_rep4 Liver, Y665H_female
GSM9286553 Liver, Y665H_female_rep5 Liver, Y665H_female
GSM9286554 Liver, Y665H_female_rep6 Liver, Y665H_female

Datasets on a similar topic

GSE310018 Disease-associated mutations on the STAT5B SH2 domain regulate cholesterol and lipid metabolism in liver 85 samples shares stat5b, sh2, disease-associated, cholesterol, mutations, regulate, domain
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, rna-seq, domain
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, rna-seq, domain
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, rna-seq, domain
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, domain
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, domain
GSE338662 STAT3 SH2 Domain Aspartic Acid 661 Mutations Activate Immune Gene Programs 18 samples shares sh2, mutations, domain
GSE290401 Reduced function of the adaptor SH2B3 promotes T1D via altered gc cytokine-regulated, T cell intrinsic immune tolerance 60 samples shares sh2, regulate

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