Single-nucleus transcriptomic profiling identifies cell types and their age-associated transcriptional changes in the glia-rich optic nerve of the African turquoise killifish

ABSTRACT: White matter dysfunction is a hallmark of brain aging and often precedes overt neurodegeneration, yet the cellular alterations connecting aging to white matter dysfunction remain poorly understood. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for aging studies, displaying rapid aging phenotypes within its four to six-month lifespan. Previous transcriptomic profiling of the aging killifish retina suggested that CNS immune and glial cells undergo more pronounced age-associated transcriptomic changes than neurons. Given the heterogeneous responses of CNS immune and glial cells to aging, we performed snRNAseq on optic nerves from young-adult (6-week-old) and aged (18-week-old) killifish. Our findings demonstrate that all expected CNS immune and glial populations are present in the optic nerve and undergo distinct aging-associated transcriptional changes. Oligodendroglia, however, displayed the most pronounced alterations, including a marked induction of IFN-associated pathways and decrease in lipid metabolism, indicating that oligodendroglial are the major agign cell population.

ORGANISM(S): Nothobranchius furzeri

PROVIDER: GSE347881 | GEO | 2026/09/23

REPOSITORIES: GEO