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Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors

GSE255135 Mus musculus (mouse) Single-cell RNA-seq 10 samples Submitted 2025/04/22 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 10 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. 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
10 samples: 3 × P2_islet_cells_repeat vs 2 × 2_month_male_islet_cells_repeat vs 2 × 2_month_female_islet_cells_repeatGroups 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
Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitorsNature communications · 2025
Summary (written by the submitters)
Endocrine islet beta cells comprise heterogenous cell subsets. Yet the origin, stability, and physiological significance of these subsets remain largely unknown. Using combinatorial cell lineage tracing, scRNA-seq, and DNA methylation analysis, we show here that embryonic islet progenitors with differential gene expression and DNA methylation produce stable beta-cell subtypes of different function and viability in adult mice.
Read the full summary ↓
Differentially expressed genes, including the Myt transcription factors, voltage-gated channels, and Ca2+-sensor synaptotagmins, contribute to the functional differences of these subtypes. Maternal overnutrition, a major diabetes risk factor, reduces the proportion of endocrine progenitors of the better-functionality beta-cell subtype. Intriguingly, the gene signature that defines mouse beta-cell subtypes can reliably divide human cells into two populations, with the proportion of better-functionality beta cells reduced in diabetic donors. These results establish that some beta-cell subtypes are determined via DNA methylation in embryonic islet progenitors, which is regulated by diabetes-causing maternal factors. The implication is that modulating DNA methylation in islet progenitors can be explored to improve beta-cell function in the prevention and therapy of diabetes.
Published in
Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors
Brown ME, Miranda VE, Nevills S et al. · Nature communications 2025 · PMID 40593675 · doi:10.1038/s41467-025-60831-0
This dataset
Open GSE255135 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 GSE255135_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 PRJNA1073578 and SRA study SRP488342. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40593675) ↗
Study design
3 × P2_islet_cells_repeat vs 2 × 2_month_male_islet_cells_repeat vs 2 × 2_month_female_islet_cells_repeat

Supports a between-group comparison across 7 samples.

How we read this: 3 replicated groups read from 10 sample titles; they account for 7 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
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