GEO series

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

GSE315101 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 27 samples Submitted 2026/07/09 Platform GPL24247Platform GPL24676

Summary

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. 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.

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Direct links to NCBI, no account and no request form: the whole study as GSE315101_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 27 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

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

NCBI GEO page ↗

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.

6 replicated groups read from 27 sample titles; they account for 23 of them. Check it against the sample list below before relying on it.

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