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Stem Cell Reports. 2018 May 8;10(5):1492-1504. doi: 10.1016/j.stemcr.2018.02.015. Epub 2018 Mar 29.

Promoting Myelin Repair through In Vivo Neuroblast Reprogramming.

Author information

1
1-Aix Marseille University, CNRS, IBDM-UMR 7288, Case 907, Parc Scientifique de Luminy, campus de Luminy, 13288 Marseille, Cedex 09, France.
2
1-Aix Marseille University, CNRS, IBDM-UMR 7288, Case 907, Parc Scientifique de Luminy, campus de Luminy, 13288 Marseille, Cedex 09, France. Electronic address: pascale.durbec@univ-amu.fr.

Abstract

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.

KEYWORDS:

OLIG2; SOX10; adult brain; cuprizone; myelin; neural stem cell; neuroblast; oligodendrocyte; remyelination; reprogramming

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