GEO series

5’tRNA-derived fragments modulate -cell homeostasis and islet macrophage activation in type 2 diabetes - transcriptomic

GSE302250 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2026/03/12 Platform GPL34475

At a glance

RNA-seq (gene expression) · mouse · 24 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: 24 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: 5'tRNA-derived fragments modulate β-cell homeostasis and islet macrophage activation in type 2 diabetesNature communications · 2026

Summary (written by the submitters)

During obesity and type 2 diabetes, pancreatic β-cells face chronic environmental stress, while islet-resident macrophages (iMACs) undergo metabolic reprogramming that exacerbates β-cell dysfunction. Stress-induced cleavage of transfer RNAs (tRNAs) generates tRNA-derived fragments (tRFs), whose role in this context is not fully understood.

Read the full summary ↓

We identify elevated levels of 5’tRFGlu(CTC) and 5’tRFGly(GCC) in β-cells and iMACs from db/db mice and in islets from type 2 diabetic (T2D) patients. Notably, 5’tRFGlu(CTC) is also induced under prediabetic conditions and inversely correlates with insulin secretion. Lipotoxic stress triggers their production via Angiogenin-mediated cleavage. Blocking 5’tRFGlu(CTC) in islets protects against β-cell apoptosis and restores insulin secretion under palmitate stress. Using a β-cell/macrophage co-culture system, we show that β-cell contact shapes a unique macrophage phenotype (iMAC-like) that shifts upon palmitate exposure—recapitulating in vivo observations. Inhibiting 5’tRFGlu(CTC) in iMAC-like cells prevents this activation switch, reduces β-cell stress, and improves insulin secretion. Mechanistically, 5’tRFGlu(CTC) interacts with RNA-binding proteins to regulate transcriptional and post-transcriptional pathways linked to immune activation, ECM remodeling, neurogenesis, and oxidative stress. Our study identifies 5’tRFs as key mediators of islet microenvironment remodeling in diabetes, offering new insights into intercellular stress signaling in metabolic disease.

Published in

5'tRNA-derived fragments modulate β-cell homeostasis and islet macrophage activation in type 2 diabetes

Cosentino C, Klein R, Menoud V et al. · Nature communications 2026 · PMID 42082525 · doi:10.1038/s41467-026-72641-z

This dataset

Open GSE302250 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 GSE302250_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 PRJNA1289725 and SRA study SRP599855. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42082525) ↗

Samples in this study

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+ 24 more — browse all 24 samples with per-sample file links →

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