{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315101/suppl/filelist.txt"],"Raw":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315101/suppl/GSE315101_RAW.tar"],"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315101/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"," Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315101"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Soluble DLK1 secreted by telomere-shortening-induced senescent microglia impairs oligodendrocyte functions and alters neuronal activity [DLK1_snRNA-seq]","description":"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.","dates":{"publication":"2026/07/09"},"accession":"GSE315101","cross_references":{"GSM":["GSM9421189","GSM9421188","GSM9421187","GSM9421186","GSM9421185","GSM9421184","GSM9421183","GSM9421182","GSM9421181","GSM9421180","GSM9421179","GSM9421178","GSM9421177","GSM9421176","GSM9421175","GSM9421174","GSM9421173","GSM9421195","GSM9421172","GSM9421194","GSM9421193","GSM9421192","GSM9421191","GSM9421190","GSM9867568","GSM9867569","GSM9867567"],"GPL":["24676","24247"],"GSE":["315101"],"taxon":["Mus musculus"," Homo sapiens"]}}