We first optimized a protocol to generate enriched in vitro cultures of control oligodendrocytes from three hPSC lines; one embryonic stem cell (ESC) line and two iPSCs (iPS1, iPS2; summarized in Fig. 1A). In brief, expansion of OLIG2+ retinoic acid‐ and purmorphamine‐treated NPCs 18 in the presence of FGF and PDGF resulted in conversion into OPCs that were positive for PDGFRα 22 over 2–4 weeks. Plate‐down and withdrawal of mitogens resulted in oligodendrocyte differentiation. Quantitative immunocytochemistry performed 1 week after differentiation (Fig. 1B–1D) revealed that cultures gave rise to a majority of O4+‐labeled oligodendendrocytes (ESC, 65.0 ± 2.4%; iPS1, 68.5 ± 6.8%; iPS2, 70.5 ± 10.8%) with a residual population of PDGFRα+‐OPCs (ESC, 10.5 ± 1.1%; iPS1, 11.6 ± 0.9%; iPS2, 20.3 ± 1.1%). Notably, O4+‐oligodendrocytes exhibited high coexpression of myelin basic protein (MBP) (ESC, 86.5 ± 6.1%; iPS1, 87.2 ± 3.9%; iPS2, 92.7 ± 3.3%) and very little overlapping PDGFRα expression (ESC, 6.1 ± 2.7%; iPS1, 7.2 ± 4.5%; iPS2, 5.4 ± 2.6%; Fig. 1E, 1F). By week 3 of differentiation, the number of O4+ cells remained at levels
