In vivo conversion of astrocytes to oligodendrocyte lineage cells in adult mice demyelinated brains by Sox2

Abstract Sox2 transcription factor has been frequently used for reprograming starting cells to neural progenitor/stem cells. In vivo administration of Sox2 in the adult mouse brain reprogrammed the transduced astrocytes to neurons. In searching for adequate cell source for repairing the myelin insults, here, we studied the possible conversion of astrocytes to oligodendrocyte lineage cells by Sox2, while an extensive demyelination exists in animal brain. Lentiviral particles expressing Sox2-GFP were injected into the corpora callosa of animals fed with cuprizone diet for 12 weeks. Transduced cells were mainly astrocytes that changed their fate to oligodendrocyte lineage cells by time. For further conformation astrocytes received the vector in culture and then transplanted to the animal brains. Tracing the fate of transplanted cells showed their conversion to oligodendrocyte lineage cells. In vitro transduced cell were also maintained in the oligodendrocyte progenitor cell (OPC) induction medium. Produced OPC-like cells were positive for specific markers. This study provides a new strategy for endogenous production of myelinating cells. After optimizing the experimental conditions for safety and feasibility, this approach may contribute into future cell based therapies in patients with white matter insults as like as those with multiple sclerosis.