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Mitochondrial double-stranded RNA triggers chronic stress in aged neurons

GSE301408 Homo sapiens (human) RNA-seq (gene expression) 100 samples Submitted 2026/07/01 Platform GPL24676Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 100 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
Homo sapiens (human)
Samples
100 samples: 35 conditions, mostly in duplicateGroups 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)
Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. We previously showed that aged neurons suffer from chronic stress that compromises cellular resiliency to new stress events; however, the cause of aging-linked chronic stress was unclear.
Read the full summary ↓
Here, we leverage directed transdifferentiation of human fibroblasts into aged neurons to determine the source of ISR activation. We demonstrate that increased accumulation of cytoplasmic double-stranded RNA (dsRNA) activates the eIF2α kinase PKR, which in turn triggers the ISR in aged neurons and leads to sequestration of dsRNA in stress granules. Aged neurons accumulate endogenous mitochondria-derived dsRNA that directly binds to PKR. This mitochondrial dsRNA leaks through damaged mitochondrial membranes and forms cytoplasmic foci in aged neurons. Finally, we demonstrate that PKR inhibition leads to the cessation of stress, resumption of cellular translation, and restoration of RNA-binding protein expression. Together, our results identify a source of RNA stress that destabilizes aged neurons and may contribute to neurodegeneration.
This dataset
Open GSE301408 in finder → Find more human 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 GSE301408_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 PRJNA1284943 and SRA study SRP596504. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
35 conditions, mostly in duplicate
Tdiff.1_Bulk-RNA-Seq ×3 Tdiff.2_Bulk-RNA-Seq ×3 Tdiff.4_Bulk-RNA-Seq ×3 Tdiff.5_Bulk-RNA-Seq ×3 iPSC-diff.1_Bulk-RNA-Seq ×3 Tdiff.1_Bulk-RNA-Seq_DMSO ×3 Tdiff.1_Bulk-RNA-Seq_PKRinh ×3 Tdiff.1_dsRNA-seq_IN ×3 +43 more

Supports a between-group comparison across 84 samples.

How we read this: 35 replicated groups read from 100 sample titles; they account for 84 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

+ 60 more — browse all 100 samples with per-sample file links →

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.