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Chunk #14 — RESULTS — Demethylation of cell type-specific genes occurs during directed differentiation

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Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
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oligodendrocyte differentiation including SKI, QKI, and OLIG2 (Aberg et al., 2006; Atanasoski et al., 2004; Zhou and Anderson, 2002) and the myelin proteins PLP1 and PMP22 (Figure 3D) was observed and reflected in the GREAT enrichments for myelination and regulation of action potentials in neurons (Figure S2A). Methylation of MYT1L was maintained during differentiation from hPSCs to NPCs, but was subsequently lost in the more mature OPCs. In contrast to the NPCs and 15 week fetal brain, DNA methylation of the PAX6 promoter region was evident in OPCs, 18–20 week fetal brain, and adult brain (Figure 3D–E). This successive gain of methylation at the PAX6 locus was consistent with oligodendroglial commitment in OPCs and the restricted neurogenic capacity of the adult brain and led to the functional enrichments for neuron fate commitment and motor neuron cell fate specification in the GREAT analysis (Figure S2B).