Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells

Oligodendrocyte dysfunction underlies many neurological disorders, but rapid assessment of mutation-specific effects in these cells has been impractical. To enable functional genetics in oligodendrocytes, here we report a highly efficient method for generating oligodendrocytes and their progenitors from mouse embryonic and induced pluripotent stem cells, independent of mouse strain or mutational status. We demonstrate that this approach, when combined with genome engineering, provides a powerful platform for the expeditious study of genotype–phenotype relationships in oligodendrocytes. The isolation and propagation of oligodendroglial cells from postnatal animals can be impractical for functional genetic studies. This study highlights the potential of a new approach to rapidly generate oligodendrocytes and their progenitors from mouse embryonic and induced pluripotent stem cells, independent of mouse strain or mutational status.