Programming Hippocampal Neural Stem/Progenitor Cells into Oligodendrocytes Enhances Remyelination in the Adult Brain after Injury

Demyelinating diseases are characterized by a loss of oligodendrocytes leading to axonal degeneration and impaired brain function. Current strategies used for the treatment of demyelinating disease such as multiple sclerosis largely rely on modulation of the immune system. Only limited treatment options are available for treating the later stages of the disease, and these treatments require regenerative therapies to ameliorate the consequences of oligodendrocyte loss and axonal impairment. Directed differentiation of adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes may represent an endogenous source of glial cells for cell-replacement strategies aiming to treat demyelinating disease. Here, we show that Ascl1-mediated conversion of hippocampal NSPCs into mature oligodendrocytes enhances remyelination in a diphtheria-toxin (DT)-inducible, genetic model for demyelination. These findings highlight the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions in the adult brain. [Display omitted] •Programming hippocampal NSPCs into oligodendrocytes follows developmental programs•Programming NSPCs into oligodendrocytes enhances remyelination after injury•Induced oligodendrocytes mature and myelinate, as shown at a single-cell level•Proof of concept for targeting hippocampal NSPCs for glial brain repair is provided Regenerative approaches for replacing lost oligodendrocytes in demyelinating disease are scant. Braun et al. show that programming adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes enhances remyelination in a genetic model of demyelination, highlighting the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions.