Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems

Rehbach, Kristina; Fernando, Michael B.; Brennand, Kristen J.

doi:10.1523/jneurosci.0518-19.2019

Cited by 15 publications

(10 citation statements)

References 134 publications

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“…As iPSC technology developed and became more accessible, researchers began to focus on less well-defined psychiatric diseases, such as bipolar disorder (Hoffmann et al 2018 ; Miller and Kelsoe 2017 ; O'Shea and McInnis 2015 ; Viswanath et al 2015 ; Watmuff et al 2016 ), alcohol use disorder (Prytkova et al 2018 ) and anorexia nervosa (Maussion et al 2019 ). There has also been a great interest in the use of 3D brain organoids instead of 2D neuronal cells, and the use of CRISPR/cas9 to genetically edit iPSC-derived models, which have been extensively reviewed elsewhere (Korhonen et al 2018 ; Lee et al 2017 ; Rehbach et al 2020 ; Tian et al 2020 ). In this systematic review, we aim to present an update of iPSC-based research into already relatively well-studied polygenic psychiatric disorders, less focusing on the syndromic and monogenetic forms, and review recent novel data on less well-studied disorders.…”

Section: Introductionmentioning

confidence: 99%

Mental health dished up—the use of iPSC models in neuropsychiatric research

et al. 2020

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Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.

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Section: Introductionmentioning

confidence: 99%

Mental health dished up—the use of iPSC models in neuropsychiatric research

et al. 2020

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“…• Knockout of genes to search for those that are directly involved in the pathogenesis of diseases or modify it [33];…”

Section: Crispr-based Systems a Tool For Studying Cell Models Of Diseasesmentioning

confidence: 99%

Creation and Research of Cell Models of Hereditary Neurodegenerative Diseases Using Directed Genome Editing

et al. 2021

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Neurodegenerative diseases make up a large part of overall morbidity around the world. In particular, an increase in the average age of the population in most developed countries leads to a drastic increase in the proportion of patients with diagnoses such as Alzheimer's disease and Parkinson's disease. The existing methods of treatment are predominantly symptomatic and, in some cases can have a pronounced clinical effect, however, they cannot prevent the continuing death of neurons or reverse neurodegenerative process. To a large extent, these problems are associated with an insufficient understanding of the molecular genetic mechanisms that underlie pathogenesis, as well as with the lack of models that allow qualitative and quantitative data on the processes occurring in the neurons of patients to be obtained. The development of technologies of induced pluripotency, directed differentiation of pluripotent cells, and gene editing using programmed nucleases, makes it possible to significantly expand the arsenal of available research tools, especially in the search for new targets for drug and gene therapy.

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“…Due to the extensive genetic variability that exists between humans, stem cell-based studies aiming to determine the neurological impacts of mutations in even a single gene have traditionally required a large number of cell lines derived from patients with the same disease (and with multiple clones per patient), as well as multiple cell lines from unaffected individuals to serve as controls. Though more recently, for diseases caused by known genetic variants or with established genotype-phenotype correlations, genome editing technologies such as CRISPR/Cas9 (reviewed in Rehbach et al, 2020 ) can efficiently establish paired gene variant and isogenic control cell lines. Thus, inbred animals are no longer the only way to model disease-related mutations across isogenic backgrounds.…”

Section: Culture Models For Neuroscience Researchmentioning

confidence: 99%

Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells

Knock

Julian

2021

Front. Cell. Neurosci.

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The brain is our most complex and least understood organ. Animal models have long been the most versatile tools available to dissect brain form and function; however, the human brain is highly distinct from that of standard model organisms. In addition to existing models, access to human brain cells and tissues is essential to reach new frontiers in our understanding of the human brain and how to intervene therapeutically in the face of disease or injury. In this review, we discuss current and developing culture models of human neural tissue, outlining advantages over animal models and key challenges that remain to be overcome. Our principal focus is on advances in engineering neural cells and tissue constructs from human pluripotent stem cells (PSCs), though primary human cell and slice culture are also discussed. By highlighting studies that combine animal models and human neural cell culture techniques, we endeavor to demonstrate that clever use of these orthogonal model systems produces more reproducible, physiological, and clinically relevant data than either approach alone. We provide examples across a range of topics in neuroscience research including brain development, injury, and cancer, neurodegenerative diseases, and psychiatric conditions. Finally, as testing of PSC-derived neurons for cell replacement therapy progresses, we touch on the advancements that are needed to make this a clinical mainstay.

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Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems

Cited by 15 publications

References 134 publications

Mental health dished up—the use of iPSC models in neuropsychiatric research

Mental health dished up—the use of iPSC models in neuropsychiatric research

Creation and Research of Cell Models of Hereditary Neurodegenerative Diseases Using Directed Genome Editing

Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells

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