Integrated omics reveals disease-associated radial glia-like cells with epigenetically dysregulated interferon response in multiple sclerosis.

ABSTRACT: Progressive multiple sclerosis (PMS) involves a persistent, maladaptive inflammatory process with numerous cellular drivers. We generated induced neural stem cells (iNSCs) from patient fibroblasts through a direct reprogramming protocol that preserved their epigenome, which revealed a PMS-specific hypomethylation of lipid metabolism and interferon (IFN) signaling genes. Single-cell multi-omics uncovered a novel, disease-associated radial glia-like cell (DARG) subpopulation in PMS cell lines exhibiting senescence and potent IFN responsiveness driven by specific transcription factors. Functionally, PMS iNSCs induced paracrine senescence and inflammation onto control cells, which was inhibited upon senolytic treatment. We identified in PMS brains a distinct population of senescent, IFN-respon

SUBMITTER: Park B 

PROVIDER: S-EPMC12834227 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature