Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms
Open accessAbstract
Schizophrenia is a neuropsychological disorder with a strong heritable component; genetic risk for schizophrenia is conferred by both common variants of relatively small effect and rare variants with high penetrance. Genetically engineered mouse models can recapitulate rare variants, displaying some behavioral defects associated with schizophrenia; however, these mouse models cannot recapitulate the full genetic architecture underlying the disorder. Patient-derived human induced pluripotent stem cells (hiPSCs) present an alternative approach for studying rare variants, in the context of all other risk alleles. Genome editing technologies, such as CRISPR-Cas9, enable the generation of isogenic hiPSC lines with which to examine the functional contribution of single variants within any genetic background. Studies of these rare variants using hiPSCs have the potential to identify commonly disrupted pathways in schizophrenia and allow for the identification of new therapeutic targets. This article is part of a Special Issue entitled SI:StemsCellsinPsychiatry.
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2D iPSC models have been important for analysing gene expression, cell morphology, neuronal excitability and synapse formation, and have shed light on mechanisms underlying schizophrenia, bipolar disorder and Rett syndrome.
“2D iPSC models have been important for analysing parameters such as gene expression, cell morphology, neuronal excitability, and synapse formation76,77 and have shed light on mechanisms underlying disorders such as schizophrenia78,79, bipolar disorder78–80, and Rett syndrome81”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [77]
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Genomic stability in reprogramming
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Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders
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From “Directed Differentiation” to “Neuronal Induction”: Modeling Neuropsychiatric Disease
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The use of brain organoids to investigate neural development and disease
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The promises and challenges of human brain organoids as models of neuropsychiatric disease
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The Genesis of Schizophrenia: An Origin Story
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Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease
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Application of CRISPR/Cas9 to the study of brain development and neuropsychiatric disease
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Self-citationInvestigation of Schizophrenia with Human Induced Pluripotent Stem Cells
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Self-citationCRISPR/Cas9 Genome Editing Approaches for Psychiatric Research
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From enhanceropathies to the epigenetic manifold underlying human cognition
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Chromosomal Microarray Analysis as First-Tier Genetic Test for Schizophrenia
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Copy number variants in psychiatric disorders
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Stem Cells for Modeling Human Disease
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Mononuclear Cells of Peripheral Blood in vitro. A Model of Antipsychotic Therapy Personalization
Grunina, M. N., Zabotina, A. M., Pchelina, M. M., Nasyrova, R. F., Sosin, D. N., Ершов, Е. Е., Taraskina, A. E., & Krupitsky, E. M. (2019) · Cell and Tissue Biology · doi:10.1134/s1990519x1901005x
Hippocampal neurogenesis in schizophrenia: Strategies for harnessing neural stem cells
Han, M.-H. (2025) · New cell · doi:10.61958/ncwq2988
- Authors
- Flaherty, E. K., & Brennand, K. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Brennand, Kristen J.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 1655
- Pages
- 283-293
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4865445
- OpenAlex
- W2179384181
- Cited by
- 19
- References
- 120
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 2
- FWCI
- 0.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Brain and Behavior Young Investigator Grant
- National Institute of Health (NIH) (R01 MH101454)
- New York Stem Cell Foundation.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- schizophrenia, copy number variation, human induced pluripotent stem cells, rare variants, isogenic cell lines, CRISPR/Cas9 genome editing, disease modeling, neuropsychiatric disorders, therapeutic target
- MeSH terms
- Animals, Mental Disorders, Humans, DNA Copy Number Variations, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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