{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315100/suppl/GSE315100_raw_counts_all_samples_DLK1_Bang.txt.gz"],"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315100/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315100"],"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(ipsc_cell)","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":"GSE315100","cross_references":{"GSM":["GSM9421149","GSM9421148","GSM9421169","GSM9421147","GSM9421146","GSM9421168","GSM9421145","GSM9421167","GSM9421166","GSM9421144","GSM9421165","GSM9421164","GSM9421163","GSM9421162","GSM9421161","GSM9421160","GSM9421159","GSM9421158","GSM9421157","GSM9421156","GSM9421155","GSM9421154","GSM9421153","GSM9421152","GSM9421151","GSM9421150","GSM9421171","GSM9421170"],"GPL":["24676"],"GSE":["315100"],"taxon":["Homo sapiens"]}}