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Review
. 2023 Apr 1;93(7):594-605.
doi: 10.1016/j.biopsych.2022.12.015. Epub 2022 Dec 24.

Development and Application of Brain Region-Specific Organoids for Investigating Psychiatric Disorders

Zhijian Zhang  1 , Xin Wang  1 , Sean Park  1 , Hongjun Song  2 , Guo-Li Ming  3
Affiliations
Review

Development and Application of Brain Region-Specific Organoids for Investigating Psychiatric Disorders

Zhijian Zhang et al. Biol Psychiatry. .

Abstract

Human society has been burdened by psychiatric disorders throughout the course of its history. The emergence and rapid advances of human brain organoid technology provide unprecedented opportunities for investigation of potential disease mechanisms and development of targeted or even personalized treatments for various psychiatric disorders. In this review, we summarize recent advances for generating organoids from human pluripotent stem cells to model distinct brain regions and diverse cell types. We also highlight recent progress, discuss limitations, and propose potential improvements in using patient-derived or genetically engineered brain region-specific organoids for investigating various psychiatric disorders.

Keywords: Brain organoids; Cellular modeling; Patient iPSC; Patterning; Psychiatric disorders.

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Conflict of interest statement

Conflict of interest statement

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1.
Figure 1.. Patient-derived brain region-specific organoids for studies of psychiatric disorders and therapeutic strategies.
(a) Human iPSCs are established from donor tissue of patients or healthy family controls. (b) Distinct brain region-specific organoids are then generated by patterning with proper morphogens based on the endogenous human brain development process using these hiPSCs. (c) Comparative analysis between patient and control organoids can be performed to reveal pathological phenotypes and mechanisms at molecular, cellular, structural, and functional levels. (d) Based on the knowledge acquired from these studies, brain region-specific organoids can be used for testing drug responses and large-scale drug screening. (e) Eventually, brain region-specific organoids can be used to develop novel and personalized therapeutic strategies for patients.
Figure 2.
Figure 2.. Genetically engineered brain organoids derived from healthy donors for functional studies of risk gene variants.
Engineered brain organoids can be used for highly efficient functional screening and in-depth phenotypic convergence studies of protein-coding risk genes and non-coding SNP variants.
See this image and copyright information in PMC

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References

    1. Insel TR, Cuthbert BN (2015): Medicine. Brain disorders? Precisely. Science. 348:499–500. - PubMed
    1. Lewis DA, Levitt P (2002): Schizophrenia as a Disorder of Neurodevelopment. Annual Review of Neuroscience. 25:409–432. - PubMed
    1. Raedler TJ, Knable MB, Weinberger DR (1998): Schizophrenia as a developmental disorder of the cerebral cortex. Current Opinion in Neurobiology. 8:157–161. - PubMed
    1. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ (2001): Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet. 69:428–433. - PMC - PubMed
    1. Brandon NJ, Sawa A (2011): Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nat Rev Neurosci. 12:707–722. - PMC - PubMed

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