Our results suggest that an interplay between DNA methylation and demethylation regulates cellular differentiation. We observed DNA methylation changes during directed differentiation of hPSCs into NPCs and OPCs that recapitulated patterns of DNA methylation at neural and oligodendrocyte-specific genes in fetal and adult brain samples, supporting the validity of hPSCs as models of development and disease. For example, dysregulation of QKI (KH domain- containing RNA binding factor “quaking homolog”), is strongly associated with schizophrenia (Aberg et al., 2006). As QKI was uniquely hypomethylated in fetal and adult brain samples in our data, the demethylation of this gene observed during neural differentiation of hPSCs may be a necessary feature for accurate in vitro modeling of schizophrenia.
