Promoting Myelin Repair through In Vivo Neuroblast Reprogramming

Abstract

Summary: Demyelination is frequently observed in a variety of CNS insults and neurodegenerative diseases. In rodents, adult neural stem cells can generate oligodendrocytes and participate to myelin repair. However, these cells mainly produce migratory neuroblasts that differentiate in the olfactory bulb. Here, we show that, in the demyelination context, a small subset of these neuroblasts can spontaneously convert into myelinating oligodendrocytes. Furthermore, we demonstrate that the contribution of neuroblasts to myelin repair can be improved by in vivo forced expression of two transcription factors: OLIG2 and SOX10. These factors promote directed fate conversion of endogenous subventricular zone neuroblasts into mature functional oligodendrocytes, leading to enhanced remyelination in a cuprizone-induced mouse model of demyelination. These findings highlight the unexpected plasticity of committed neuroblasts and provide proof of concept that they could be targeted for the treatment of demyelinated lesions in the adult brain. : Durbec and colleagues highlight the fate plasticity of neuroblasts in mouse brain after demyelination. They show that a subset of neuroblasts produced in SVZ spontaneously convert into oligodendrocytes after demyelination. They furthermore demonstrate that myelin regeneration can be enhanced by forcing this spontaneous conversion through in-vivo-directed cell reprogramming by forced expression of Olig2 and Sox10 in endogenous neuroblasts. Keywords: adult brain, myelin, neural stem cell, neuroblast, oligodendrocyte, reprogramming, cuprizone, remyelination, OLIG2, SOX10