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. 2020 Apr 22;9(4):1037. doi: 10.3390/cells9041037

Figure 7.

Figure 7

c-Rel inhibition drives hNSCs switch from neuronal to oligodendroglial phenotype. Upper panel: NCSCs are specified to NSCs, and differentiate upon neuronal induction into glutamatergic neurons. Cells undergo a strong increase in nuclear c-REL during early differentiation in the absence of PTXF, that induces a specific gene program expression towards the neuronal fate. Confirmed by an increased in mature neuronal markers NF200 and VGLUT2, and a strong reduction in O4, the absence of GFAP and OLIG2 accompanied by a strong survival, whereas PTXF-treated differentiated NSCs had no increase in nuclear c-REL, leading to a shift in the cell fate into the oligodendrocyte lineage. This was confirmed by a clear increase in oligodendrocyte markers OLIG2 and O4, and a strong reduction in neuronal markers (NF200, VGLUT2), and also accompanied by a strong reduction in cell survival. Bottom panel: Transplantation of PTXF-treated predifferentiated NSCs into a demyelination mouse organotypic cerebellar slice model further demonstrated their capability to differentiate into MBP+ oligodendrocytes and produce myelin ex vivo. Cells exhibited a clear oligodendroglial phenotype and differentiated into huNu+/MBP+ oligodendrocytes after 14 days of cocultivation. PTXF: pentoxifylline, NCSCs: neural crest-derived stem cells, NSCs: neural stem cells.