GEO series

HNF1A regulates a β-cell RNA splicing program that is disrupted in type 2 diabetes [RNA-seq]

GSE277551 Homo sapiens (human) Single-cell RNA-seq 17 samples Submitted 2025/08/03 Platform GPL24676Platform GPL21103

At a glance

Single-cell RNA-seq · human · 17 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: Homo sapiens (human)
Samples: 17 samples: 5 conditions, mostly in triplicateGroups 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: HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetesCell metabolism · 2025

Summary (written by the submitters)

Type 2 diabetes (T2D) is a complex chronic disease that results from pancreatic β-cell dysfunction and insulin resistance. Human genetic evidence supports a pivotal role of HNF1A, encoding hepatocyte nuclear factor 1A, in the pathophysiology of mendelian and type 2 diabetes. Recent single-cell genomic studies also reveal HNF1A as a key transcription factor underlying β-cell heterogeneity and disease progression.

Read the full summary ↓

We now demonstrate that HNF1A-deficient diabetes is caused by β-cell-autonomous defects, and show that HNF1A governs not only β-cell transcription, but also a broad RNA splicing program. We uncover a regulatory hierarchy in which HNF1A controls transcription of A1CF, which in turn regulates splicing of genes important for membrane transport, lysosome, and secretory functions. Genetic variants that increase human pancreatic islet A1CF expression are associated with improved glycemia, increased insulin secretion, and decreased T2D susceptibility. Furthermore, β-cells from T2D individuals exhibit a profound disruption of A1CF-dependent splicing. These findings link HNF1A-deficiency to a β-cell RNA splicing defect that is impaired in Mendelian diabetes and T2D.

Published in

HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes

Bernardo E, De Vas MG, Balboa D et al. · Cell metabolism 2025 · PMID 40774250 · doi:10.1016/j.cmet.2025.07.007

This dataset

Open GSE277551 in finder → Find more 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 GSE277551_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 PRJNA1162791 and SRA study SRP533589. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40774250) ↗

Study design

5 conditions, mostly in triplicate

Hnf1a WT mouse islets Control ×4 Hnf1a KO mouse islets NS ×4 Control EndoC-BH3 ×3 HNF1A KO EndoC-BH3 ×3 A1CF KO EndoC-BH3 ×3

Supports a between-group comparison across 17 samples.

How we read this: 5 replicated groups read from 17 sample titles; they account for 17 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

GSM8524406 Hnf1a WT mouse islets Control 1 Hnf1a WT mouse islets C…
GSM8524407 Hnf1a WT mouse islets Control 2 Hnf1a WT mouse islets C…
GSM8524408 Hnf1a WT mouse islets Control 3 Hnf1a WT mouse islets C…
GSM8524409 Hnf1a WT mouse islets Control 4 Hnf1a WT mouse islets C…
GSM8524410 Hnf1a KO mouse islets NS 1 Hnf1a KO mouse islets NS
GSM8524411 Hnf1a KO mouse islets NS 2 Hnf1a KO mouse islets NS
GSM8524412 Hnf1a KO mouse islets NS 3 Hnf1a KO mouse islets NS
GSM8524413 Hnf1a KO mouse islets NS 4 Hnf1a KO mouse islets NS
GSM8524414 Control EndoC-BH3 1 Control EndoC-BH3
GSM8524415 Control EndoC-BH3 2 Control EndoC-BH3
GSM8524416 Control EndoC-BH3 3 Control EndoC-BH3
GSM8524417 HNF1A KO EndoC-BH3 1 HNF1A KO EndoC-BH3
GSM8524418 HNF1A KO EndoC-BH3 2 HNF1A KO EndoC-BH3
GSM8524419 HNF1A KO EndoC-BH3 3 HNF1A KO EndoC-BH3
GSM8524420 A1CF KO EndoC-BH3 1 A1CF KO EndoC-BH3
GSM8524421 A1CF KO EndoC-BH3 2 A1CF KO EndoC-BH3
GSM8524422 A1CF KO EndoC-BH3 3 A1CF KO EndoC-BH3

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.