Here we review schizophrenia-relevant cellular phenotypes modelled in patient-derived hiPSCs.
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Neurodevelopmental, synaptic and mitochondrial pathologies were consistently reported across studies.
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Precise modelling of schizophrenia pathogenesis could benefit from advances in genome editing and brain organoid culture.
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We also discuss the future challenges in modeling cellular phenotypes of schizophrenia.
Abstract
Schizophrenia is one of the leading causes of disability among mental disorders, contributing to a substantial socioeconomic burden. Our understanding of the mechanisms of the pathogenesis of the disease has largely been limited by its inherent complexity imparted by the polygenicity and interactions with environmental factors. Since pathobiological events are initiated in the schizophrenic brain long before the onset of the psychotic manifestations, characterizing these processes is limited, mainly due to a lack of access to neuronal tissues. Induced pluripotent stem cell (iPSC) technologies have provided an unprecedented opportunity to establish pluripotent stem cells from patients with schizophrenia and differentiate them into neuronal lineage, enabling an in vitro recapitulation of the pathogenesis of the disease. Despite the inherent challenges, patient-derived iPSC studies of schizophrenia have been instrumental in unraveling the cellular and molecular phenotypes that might be involved in the biological causality. Here we review the literature and focus on studies that have utilized patient-derived iPSCs to model the pathogenesis of schizophrenia. We also discuss the challenges in modeling cellular phenotypes of schizophrenia.
