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Uncontrolled endoplasmic reticulum stress response leads to pancreatic beta cell death via JNK andp53

GSE282680 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2026/05/27 Platform GPL21103
At a glance

RNA-seq (gene expression) · mouse · 16 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
16 samples: 16 samples, each with a distinct title — no replicated groupsGroups 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.
Summary (written by the submitters)
Endoplasmic reticulum (ER) stress is a cause of beta cell death in both T1D and T2D. However, no therapeutics to reduce beta cell death have been approved, in part because molecular mechanisms driving beta cell death during ER stress are insufficiently defined. GRP78, an ER chaperone, is the critical regulator of unfolded protein response (UPR) stress response pathways.
Read the full summary ↓
GRP78 binds and suppresses UPR initiators during the unstressed state, releasing them to promote UPR activation during stress. To study pathways causing beta cell decompensation during active ER stress and the related stress response, we engineered mice genetically lacking GRP78 in pancreatic beta cells. GRP78 deletion caused acute insulin deficient diabetes in pups before weaning, with reduced beta cell mass due to increased apoptosis. Molecular studies identified deregulated UPR, specifically IRE1 activity, as driving cell death. Unbiased and targeted analyses outline a pathway in which JNK activity downstream of IRE1 kinase leads to p53 activation to mediate beta cell death during ER stress. Remarkably, in vivo JNK inhibition reduced beta cell death in two distinct ER stress diabetes models. In human beta cells, inhibitors of JNK and of p53 were both effective to improve beta cell survival in the face of ER stress. Our findings provide insight into mechanisms causing beta cell death and outline possible therapeutic targets to preserve insulin secretory capacity in the face of ER stress.
This dataset
Open GSE282680 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 GSE282680_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 PRJNA1189605 and SRA study SRP547360. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
16 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 8 samples read as cases, 8 as controls.

How we read this: Read from 16 sample titles: 16 distinct titles with little repetition. 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
Datasets on a similar topic

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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.