Stephanie J Temme1, Brady J Maher2, Kimberly M Christian3. 1. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 2. Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 3. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abstract
PURPOSE OF REVIEW: Induced pluripotent stem cells (iPSCs) can be generated from human patient tissue samples, differentiated into any somatic cell type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies. RECENT FINDINGS: Results from patient specific-iPSC studies often reveal cellular phenotypes consistent with postmortem and brain imaging studies. Unpredicted findings illustrate the power of iPSCs as a discovery tool, but may also be attributable to limitations in modeling dynamic neural networks or difficulty in identifying the most affected neural subtype or developmental stage. SUMMARY: Technological advances in differentiation protocols and organoid generation will enhance our ability to model the salient pathology underlying psychiatric disorders using iPSCs. The field will also benefit from context-driven interpretations of iPSC studies that recognize all potential sources of variability, including differences in patient symptomatology, genetic risk factors and affected cellular subtype.
PURPOSE OF REVIEW: Induced pluripotent stem cells (iPSCs) can be generated from humanpatient tissue samples, differentiated into any somatic cell type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies. RECENT FINDINGS: Results from patient specific-iPSC studies often reveal cellular phenotypes consistent with postmortem and brain imaging studies. Unpredicted findings illustrate the power of iPSCs as a discovery tool, but may also be attributable to limitations in modeling dynamic neural networks or difficulty in identifying the most affected neural subtype or developmental stage. SUMMARY: Technological advances in differentiation protocols and organoid generation will enhance our ability to model the salient pathology underlying psychiatric disorders using iPSCs. The field will also benefit from context-driven interpretations of iPSC studies that recognize all potential sources of variability, including differences in patient symptomatology, genetic risk factors and affected cellular subtype.
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