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Soluble DLK1 secreted by telomere-shortening-induced senescent microglia impairs oligodendrocyte functions and alters neuronal activity [DLK1_snRNA-seq]

GSE315101 Homo sapiens (human) Single-nucleus RNA-seq 27 samples Submitted 2026/07/09 Platform GPL24247Platform GPL24676
At a glance

Single-nucleus RNA-seq · human · 27 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue).
Organism
Homo sapiens (human)
Samples
27 samples: 6 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.
Summary (written by the submitters)
Aging is a predominant risk factor of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Here, we investigated the impact of telomere shortening, a physiological hallmark of aging, on brain function. Telomere-shortened mice exhibited cognitive decline and exacerbated lipofuscinosis, accompanied by the emergence of senescent microglia with a senescence-associated secretory phenotype and oligodendrocyte lineage cells with impaired maturation.
Read the full summary ↓
Using iPSC-derived microglia with shortened telomeres, we identified DLK1 as a novel senescence-associated ligand secreted by senescent microglia. Elevated soluble DLK1 was detected in the cerebrospinal fluid of both telomere-shortened and physiologically aged mice, and this increase was abolished by microglial depletion, confirming its microglial origin. Functionally, AAV-mediated expression of sDLK1 in mouse brains induced hypomyelination and disrupted oligodendrocyte differentiation in vivo. In human iPSC-derived systems, sDLK1 impaired late-stage oligodendrocyte maturation and disrupted neuronal calcium signaling. Together, these findings establish replicative microglial senescence as a pathological feature of telomere shortening and identify sDLK1 as one key effector linking senescent microglia to oligodendrocyte dysfunction and neuronal dysregulation during brain aging.
This dataset
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.

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 GSE315101_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1394999 and SRA study SRP658561. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
LG180 ×8 Ctrl ×3 sDLK ×3 LG145 ×3 WT_F ×3 LG107 ×3 Mouse ×1 Mouse_F ×1 +2 more

Supports a between-group comparison across 23 samples.

How we read this: 6 replicated groups read from 27 sample titles; they account for 23 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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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.