From cells to insights: the power of human pluripotent stem cell-derived cortical interneurons in psychiatric disorder modeling

Abstract

Psychiatric disorders, such as schizophrenia (SCZ) and autism spectrum disorders (ASD), represent a global health challenge with their poorly understood and complex etiologies. Cortical interneurons (cINs) are the primary inhibitory neurons in the cortex and their subtypes, especially those that are generated from the medial ganglionic emission (MGE) region, have been shown to play an important role in the pathogenesis of these psychiatric disorders. Recent advances in induced pluripotent stem cell (iPSC) technologies provide exciting opportunities to model and study these disorders using human iPSC-derived cINs. In this review, we present a comprehensive overview of various methods employed to generate MGE-type cINs from human iPSCs, which are mainly categorized into induction by signaling molecules vs. direct genetic manipulation. We discuss their advantages, limitations, and potential applications in psychiatric disorder modeling to aid researchers in choosing the appropriate methods based on their research goals. We also provide examples of how these methods have been applied to study the pathogenesis of psychiatric disorders. In addition, we discuss ongoing challenges and future directions in the field. Overall, iPSC-derived cINs provide a powerful tool to model the developmental pathogenesis of psychiatric disorders, thus aiding in uncovering disease mechanisms and potential therapeutic targets. This review article will provide valuable resources for researchers seeking to navigate the complexities of cIN generation methods and their applications in the study of psychiatric disorders.

Keywords: GABAergic neurons; gene editing; in vitro techniques; induced pluripotent stem cells; interneurons; mental disorders; neurodevelopmental disorders; signal transduction.