Researchers used direct reprogramming to convert skin fibroblasts from progressive multiple sclerosis (PMS) patients into induced neural stem cells (iNSCs), preserving the epigenetic memory of the donor cells. Whole-genome bisulfite sequencing revealed PMS-specific hypomethylation at lipid metabolism and interferon signaling genes. Single-cell multi-omics uncovered a novel disease-associated radial glia-like cell (DARG) subpopulation marked by senescence and heightened interferon responsiveness. PMS iNSCs also induced paracrine senescence in healthy control cells, an effect reversed by the senolytic drug ABT-263 (navitoclax). Post-mortem brain analysis confirmed DARGs in chronic active MS lesions, spatially co-localizing with inflammatory glia, suggesting they sustain smoldering neuroinflammation and represent a previously unrecognized therapeutic target.
