In vivo conversion of astrocytes into oligodendrocyte lineage cells with transcription factor Sox10; Promise for myelin repair in multiple sclerosis.

Abstract

Recent studies demonstrate that astroglial cells can be directly converted into functional neurons or oligodendrocytes. Here, we report that a single transcription factor Sox10 could reprogram astrocytes into oligodendrocyte-like cells, in vivo. For transdifferentiation, Sox10-GFP expressing viral particles were injected into cuprizone-induced demyelinated mice brains after which we assessed for the presence of specific oligodendrocyte lineage cell markers by immunohistofluorescence (IHF). As control, another group of demyelinated mice received GFP expressing viral particles. After 3 weeks, the majority of transduced (GFP+) cells in animals which received control vector were astrocytes, while in animals which received Sox10-GFP vector, the main population of GFP+ cells were positive for oligodendrocyte lineage markers. We also extracted primary astrocytes from mouse pups and purified them. Primary astrocytes were transduced in vitro and then transplanted into demyelinated brains for later fate mapping. After three weeks, in vitro transduced and then transplanted astrocytes showed oligodendrocyte progenitor and mature oligodendrocyte markers. Further confirmation was done by transduction of astrocytes with lentiviral particles that expressed Sox10 and GFP and their culture in the oligodendrocyte progenitor medium. The induced cells expressed oligodendrocyte progenitor cells (iOPCs) markers. Our findings showed the feasibility of reprogramming of astrocytes into oligodendrocyte-like cells in vivo, by using a single transcription factor, Sox10. This finding suggested a master regulatory role for Sox10 which enabled astrocytes to change their fate to OPC-like cells and establish an oligodendroglial phenotype. We hope this approach lead to effective myelin repair in patients suffering from myelination deficit.