Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells
Abstract Schizophrenia (SZ) is a severe psychiatric disorder, with a prevalence of 1–2% world-wide and substantial health- and social care costs. The pathology is influenced by both genetic and environmental factors, however the underlying cause still remains elusive. SZ has symptoms including delus...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Acta Neuropathologica Communications |
| Online Access: | https://doi.org/10.1186/s40478-022-01460-2 |
| _version_ | 1811198335789301760 |
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| author | Ugne Dubonyte Andrea Asenjo-Martinez Thomas Werge Kasper Lage Agnete Kirkeby |
| author_facet | Ugne Dubonyte Andrea Asenjo-Martinez Thomas Werge Kasper Lage Agnete Kirkeby |
| author_sort | Ugne Dubonyte |
| collection | DOAJ |
| description | Abstract Schizophrenia (SZ) is a severe psychiatric disorder, with a prevalence of 1–2% world-wide and substantial health- and social care costs. The pathology is influenced by both genetic and environmental factors, however the underlying cause still remains elusive. SZ has symptoms including delusions, hallucinations, confused thoughts, diminished emotional responses, social withdrawal and anhedonia. The onset of psychosis is usually in late adolescence or early adulthood. Multiple genome-wide association and whole exome sequencing studies have provided extraordinary insights into the genetic variants underlying familial as well as polygenic forms of the disease. Nonetheless, a major limitation in schizophrenia research remains the lack of clinically relevant animal models, which in turn hampers the development of novel effective therapies for the patients. The emergence of human induced pluripotent stem cell (hiPSC) technology has allowed researchers to work with SZ patient-derived neuronal and glial cell types in vitro and to investigate the molecular basis of the disorder in a human neuronal context. In this review, we summarise findings from available studies using hiPSC-based neural models and discuss how these have provided new insights into molecular and cellular pathways of SZ. Further, we highlight different examples of how these models have shown alterations in neurogenesis, neuronal maturation, neuronal connectivity and synaptic impairment as well as mitochondrial dysfunction and dysregulation of miRNAs in SZ patient-derived cultures compared to controls. We discuss the pros and cons of these models and describe the potential of using such models for deciphering the contribution of specific human neural cell types to the development of the disease. |
| first_indexed | 2024-04-12T01:29:42Z |
| format | Article |
| id | doaj.art-799f7fcde1984dc98bf14b2f1ed66808 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-12T01:29:42Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-799f7fcde1984dc98bf14b2f1ed668082022-12-22T03:53:32ZengBMCActa Neuropathologica Communications2051-59602022-12-0110112010.1186/s40478-022-01460-2Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cellsUgne Dubonyte0Andrea Asenjo-Martinez1Thomas Werge2Kasper Lage3Agnete Kirkeby4Department of Neuroscience and Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of CopenhagenDepartment of Neuroscience and Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of CopenhagenInstitute of Biological Psychiatry, Mental Health Services, Copenhagen University HospitalInstitute of Biological Psychiatry, Mental Health Services, Copenhagen University HospitalDepartment of Neuroscience and Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of CopenhagenAbstract Schizophrenia (SZ) is a severe psychiatric disorder, with a prevalence of 1–2% world-wide and substantial health- and social care costs. The pathology is influenced by both genetic and environmental factors, however the underlying cause still remains elusive. SZ has symptoms including delusions, hallucinations, confused thoughts, diminished emotional responses, social withdrawal and anhedonia. The onset of psychosis is usually in late adolescence or early adulthood. Multiple genome-wide association and whole exome sequencing studies have provided extraordinary insights into the genetic variants underlying familial as well as polygenic forms of the disease. Nonetheless, a major limitation in schizophrenia research remains the lack of clinically relevant animal models, which in turn hampers the development of novel effective therapies for the patients. The emergence of human induced pluripotent stem cell (hiPSC) technology has allowed researchers to work with SZ patient-derived neuronal and glial cell types in vitro and to investigate the molecular basis of the disorder in a human neuronal context. In this review, we summarise findings from available studies using hiPSC-based neural models and discuss how these have provided new insights into molecular and cellular pathways of SZ. Further, we highlight different examples of how these models have shown alterations in neurogenesis, neuronal maturation, neuronal connectivity and synaptic impairment as well as mitochondrial dysfunction and dysregulation of miRNAs in SZ patient-derived cultures compared to controls. We discuss the pros and cons of these models and describe the potential of using such models for deciphering the contribution of specific human neural cell types to the development of the disease.https://doi.org/10.1186/s40478-022-01460-2 |
| spellingShingle | Ugne Dubonyte Andrea Asenjo-Martinez Thomas Werge Kasper Lage Agnete Kirkeby Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells Acta Neuropathologica Communications |
| title | Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells |
| title_full | Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells |
| title_fullStr | Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells |
| title_full_unstemmed | Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells |
| title_short | Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells |
| title_sort | current advancements of modelling schizophrenia using patient derived induced pluripotent stem cells |
| url | https://doi.org/10.1186/s40478-022-01460-2 |
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