Human-induced pluripotent stem cell-derived neural cells to model epigenetic regulations in the nervous system and brain disorders in vitro.

Epigenetic regulations, including DNA methylation, histone modification, and noncoding RNA regulation, play essential roles in human diseases but our understanding of their involvement in central nervous system disorders has been hampered by the complexity of the human brain and the inaccessibility of targeted cells. Previously, disease-relevant neural cell types were only available from postmortem tissues after many years of disease progression and potential exposure to many different medications. Human-induced pluripotent stem cells (iPSCs) generated by cellular reprogramming of somatic cells have provided promising in vitro disease models to enable the study of brain disorders at molecular and cellular levels that were previously impossible. Recent methodological advances in molecular biology and genomics technologies enable researchers to investigate epigenetic regulations using iPSC-derived neural models, which is expected to have a great impact on understanding the pathophysiology of neurodevelopmental and neurodegenerative disorders and expand future therapeutic possibilities. In this chapter, we review the current understanding of epigenetic regulation in neurodevelopmental and neurodegenerative disorders, focusing on the potential of human iPSC-derived neural models as promising tools for the epigenetic study of these disorders.