Human Stem Cell Models of Neurodevelopmental Disorders

Developments in stem cell and developmental biology have provided opportunities not only to produce human cell types affected by different diseases, but also to replay different aspects of development and tissue assembly in vitro. This chapter reviews the current status of the field in terms of progress in modeling human brain development in vitro and its application to the study of the etiology and pathogenesis of neurodevelopmental disorders. Neural stem cell (NSC) lines have been derived from postmortem fetal brains, theoretically allowing for a long-term renewable source of neuronal cell types. The chapter discusses the key milestones that have been achieved and current approaches that are used for generating pluripotent stem cells. It discusses efforts to model neurodevelopmental disorders using cerebral cortex as the main example. Alternative approaches to generating forebrain neurons and circuits are direct differentiation from PSCs and transdifferentiation from somatic cell types.