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DLK-dependent protein network regulates hippocampal glutamatergic neuron degeneration

GSE266662 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2025/01/16 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 14 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
14 samples: 4 × hippocampal glutamatergic neurons, DLK(cKO), biol vs 4 × hippocampal glutamatergic neurons, DLK WT (cKO sib), biol vs 3 × hippocampal glutamatergic neurons, DLK(iOE), biol vs 3 × hippocampal glutamatergic neurons, DLK WT (iOE sib), biolGroups 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
Translatome analysis reveals cellular network in DLK-dependent hippocampal glutamatergic neuron degenerationeLife · 2025
Summary (written by the submitters)
The conserved MAPKKK DLK plays many roles in neuronal development, axon injury, and neuronal stress responses. The outcomes of activating or inhibiting DLK signaling depend on cell-type and cellular contexts. Emerging evidence has implicated DLK signaling in several neurodegenerative diseases. However, our understanding of the DLK-dependent cellular network in the central nervous system remains limited.
Read the full summary ↓
Here, we investigated roles of DLK in hippocampal glutamatergic neurons, using conditional knockout and overexpression mice. We find that dorsal CA1 and dentate gyrus neurons are particularly vulnerable to elevated DLK activity. We performed RiboTRAP-seq analysis and identified the DLK dependent translatome, majority of which are involved in neuronal developmental processes, neuronal stress responses, and synapse formation and function. Increasing DLK signaling is associated with disruptions of microtubules, potentially involving Stmn4. We also show that in primary hippocampal neurons DLK regulates neurite outgrowth, axon specification, and synapse formation. This study broadens our understanding of both conserved and cell-type specific effects of DLK signaling. The identification of translational targets of DLK in glutamatergic neurons has relevance to our understanding of neurodegenerative disease.
Published in
Translatome analysis reveals cellular network in DLK-dependent hippocampal glutamatergic neuron degeneration
Ritchie EM, Acar D, Zhong S et al. · eLife 2025 · PMID 40067879 · doi:10.7554/eLife.101173
This dataset
Open GSE266662 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 GSE266662_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 PRJNA1108218 and SRA study SRP505918. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40067879) ↗
Study design
4 × hippocampal glutamatergic neurons, DLK(cKO), biol vs 4 × hippocampal glutamatergic neurons, DLK WT (cKO sib), biol vs 3 × hippocampal glutamatergic neurons, DLK(iOE), biol vs 3 × hippocampal glutamatergic neurons, DLK WT (iOE sib), biol

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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
Datasets on a similar topic

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