Opportunities and limitations for studying neuropsychiatric disorders using patient-derived induced pluripotent stem cells

ABSTRACT Neuropsychiatric disorders affect a large proportion of the global population and there is an urgent need to understand the pathogenesis and to develop novel and improved treatments

of these devastating disorders. However, the diverse symptomatology combined with complex polygenic etiology, and the limited access to disorder-relevant cell types in human brains

represent a major obstacle for mechanistic disease research. Conventional animal models, such as rodents, are limited by inherent species differences in brain development, architecture, and

function. Advances in human induced pluripotent stem cells (hiPSCs) technologies have provided platforms for new discoveries in neuropsychiatric disorders. First, hiPSC-based disease models

enable unprecedented investigation of psychiatric disorders at the molecular, cellular, and structural levels. Second, hiPSCs derived from patients with known genetics, symptoms, and drug

response profiles offer an opportunity to recapitulate pathogenesis in relevant cell types and provide novel approaches for understanding disease mechanisms and for developing effective

treatments. Third, genome-editing technologies have extended the potential of hiPSCs for generating models to elucidate the genetic basis of rare monogenetic and complex polygenic

psychiatric disorders and to establish the causality between genotype and phenotype. Here we review opportunities and limitations for studying psychiatric disorders using various

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INDUCED PLURIPOTENT STEM CELL (IPSC) LINES INCLUDING CLINICAL, GENOMIC, AND CELLULAR DATA FROM GENETICALLY ISOLATED FAMILIES WITH MOOD AND PSYCHOTIC DISORDERS Article Open access 16 December

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FUNDING Funding The research in the authors’ laboratory were supported by grants from the Institutes of Health (R35NS097370, U19AI131130, RF1MH123979, R01MH125528 to GLM, and R35NS116843,

U01HG012047, RF1AG079557, and U19MH106434 to H.S.) and from Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to GLM). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department

of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Yan Hong, Qian Yang, Hongjun Song & Guo-li Ming *

Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Hongjun Song & Guo-li Ming * Institute for Regenerative

Medicine, University of Pennsylvania, Philadelphia, PA, USA Hongjun Song & Guo-li Ming * The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia,

PA, USA Hongjun Song * Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Guo-li Ming Authors * Yan Hong View author publications You

can also search for this author inPubMed Google Scholar * Qian Yang View author publications You can also search for this author inPubMed Google Scholar * Hongjun Song View author

publications You can also search for this author inPubMed Google Scholar * Guo-li Ming View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS YH

wrote the manuscript with contributions from all co-authors. CORRESPONDING AUTHOR Correspondence to Guo-li Ming. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing

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ARTICLE CITE THIS ARTICLE Hong, Y., Yang, Q., Song, H. _et al._ Opportunities and limitations for studying neuropsychiatric disorders using patient-derived induced pluripotent stem cells.

_Mol Psychiatry_ 28, 1430–1439 (2023). https://doi.org/10.1038/s41380-023-01990-8 Download citation * Received: 21 September 2022 * Revised: 27 January 2023 * Accepted: 31 January 2023 *

Published: 13 February 2023 * Issue Date: April 2023 * DOI: https://doi.org/10.1038/s41380-023-01990-8 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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