Understanding neurodevelopmental disorders using human pluripotent stem cell‐derived neurons

• Published in: Brain pathology (Zurich, Switzerland) Vol. 27; no. 4; pp. 508 - 517
• Main Authors: Tamburini, Claudia, Li, Meng
• Format: Journal Article
• Language: English
• Published: Switzerland John Wiley & Sons, Inc 01.07.2017; John Wiley and Sons Inc
• Subjects: Animals; Autism; Behavior disorders; Bipolar disorder; CRISPR; Differentiation; Disease control; disease modeling; Disorders; Editing; Etiology; Genetic engineering; Genome editing; Genomes; human pluripotent stem cells; Humans; In vitro methods and tests; Induced Pluripotent Stem Cells - physiology; Induced Pluripotent Stem Cells - transplantation; Inhibitory postsynaptic potentials; Mental disorders; MINI‐SYMPOSIUM: USING iPSCs TO UNDERSTAND HUMAN NEUROLOGICAL DISEASE: POTENTIAL AND LIMITATIONS; Modelling; neurodevelopment; Neurodevelopmental disorders; Neurodevelopmental Disorders - surgery; neuronal differentiation; Neurons; Neurons - physiology; Neurons - transplantation; Pathology; Pluripotency; psychiatric disorders; Reviews; Risk; Schizophrenia; Stem cells; human pluripotent stem cells; neurodevelopment; neuronal differentiation; disease modeling; psychiatric disorders
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/bpa.12517

Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient‐specific cells, which in principle can be differentiated into all disease‐relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs‐based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference “control” hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments.