{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313031/"]},"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=GSE313031"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"LRRK2-G2019S Impairs Astrocyte Differentiation and Triggers a senescence-like phenotype in Parkinson's Disease Models - Midbrain organoids","description":"Astrocytes are increasingly recognised as essential contributors to both physiological brain function and neurodegenerative diseases. Here, we describe how the Parkinson’s disease (PD)-associated mutation LRRK2-G2019S affects astrocytes using autoptic brain samples and PD patient-specific 3D midbrain organoids and 2D astrocytes derived from induced pluripotent stem cells. In autoptic midbrain samples from LRRK2-G2019S patients, we observed a reduction in GFAP⁺ astrocytes but increased branching, together with transcriptional signatures consistent with altered astrocyte function. We also observed delayed astrocyte differentiation in PD patient-specific midbrain organoids, accompanied by altered astrocyte transcriptomic profiles revealed by single-cell RNA sequencing. This defective differentiation contributes to the acquisition of a senescent-like phenotype. In 2D cultures, astrocyte differentiation from LRRK2-G2019S precursor cells was associated with early apoptosis and altered Wnt/β-catenin and TGFβ signalling compared to LRRK2-WT cultures. Notably, pharmacological activation of the developmental transcription factor NR2F1, downregulated in LRRK2-G2019S models, reduced astrocyte cell death and senescence-like phenotypes. Together, these data show that LRRK2-G2019S impairs astrocyte specification and predisposes to a senescent phenotype.","dates":{"publication":"2026/05/19"},"accession":"GSE313031","cross_references":{"GSM":["GSM9359395","GSM9359384","GSM9359396","GSM9359385","GSM9359386","GSM9359397","GSM9359398","GSM9359387","GSM9359399","GSM9359388","GSM9359389","GSM9359400","GSM9359390","GSM9359391","GSM9359392","GSM9359393","GSM9359383","GSM9359394"],"GPL":["24676"],"GSE":["313031"],"taxon":["Homo sapiens"]}}