Brain organoids

Glass, Madison R.; Kyere, Felix A.; French, Deborah L.; Stein, Jason L.; Waxman, Elisa A.

doi:10.1016/b978-0-12-822277-5.00005-5

Cited by 3 publications

(2 citation statements)

References 144 publications

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“…The regional differences between TL and FL might also affect gene expression in specific cell types, and in turn these might impact important functional processes dysregulated in neuropsychiatric disorders. For example, region-specific characteristics of neurons in the cortex, including different electrophysiological features, have been previously reported 13 , and region-specific transcriptomic changes in neurons from the cerebral cortex (and the subcortical region) showed specific patterns of molecular and developmental regulation 13 . Cellular level differences between brain regions might be also relevant to disease pathobiology; e.g., excitatory and inhibitory neurons in the middle frontal gyrus showed a significant association with neuropsychiatric disorders 14 , and further cell type and brain area associations have been reported for depressive disorder 15 .…”

Section: Introductionmentioning

confidence: 99%

Decoding frontotemporal and cell type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs

Chao

Chen

et al. 2022

Preprint

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Abnormalities in temporal and frontal lobes (TL and FL) have been linked to cognition and neuropsychiatric disorders. While structural and functional differences between the brain lobes have been documented in disease, the cellular heterogeneity in FL and TL and its impact to the vulnerability to genetic risk factors for neuropsychiatric disorders is not well studied. We hypothesize that intrinsic cellular-level differences between TL and FL explain the vulnerability of specific cell types to genetic risk factors and psychoactive drugs. To test this, we integrated single-nucleus transcriptome analysis in fresh human FL and TL with data related to genetic susceptibility and gene dysregulation in neuropsychiatric disease, and response to psychoactive drugs. We also investigate how these differences are associated with gene dysregulation in disease brain. Neuronal cell populations were the most vulnerable to psychiatric genetic risk factors, and more specifically parvalbumin interneurons (PVALB neurons). These PVALB-expressed genetic risk factors were mostly upregulated in the TL compared with FL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. We found GRIN2A and HCN1, implicated in schizophrenia by genome-wide association studies, to be significantly upregulated in PVLAB from the TL and in brain cortex from schizophrenia patients. Our analysis provides comprehensive evidence for PVALB neurons as the most vulnerable cell type that is implicated in several psychiatric disorders. PVALB neurons showed the highest vulnerability to psychoactive drug response, which was 3.6-fold higher than the vulnerability to genetic risk factors. In summary, we show high vulnerability of PVALB neurons that is specific to the temporal lobe, implying that differences between TL and FL greatly influence the cell vulnerability to genetic risk factors as well as the response to psychoactive drugs. These findings offer insights into how regional brain differences affect the cell type vulnerabilities in neuropsychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

Decoding frontotemporal and cell type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs

Chao

Chen

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…The regional differences between TL and FL might also affect gene expression in specific cell types, and, in turn, these might impact important functional processes dysregulated in neuropsychiatric disorders. For example, region-specific characteristics of neurons in the cortex, including different electrophysiological features, have been previously reported [ 13 ], and region-specific transcriptomic changes in neurons from the cerebral cortex (and the subcortical region) showed specific patterns of molecular and developmental regulation [ 13 ]. Cellular level differences between brain regions might also be relevant to disease pathobiology; e.g.…”

Section: Introductionmentioning

confidence: 99%

Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs

Ji,

Chao,

Chen

et al. 2024

Open Biol.

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Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in ‘fresh’ human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients’ brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.

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Microinstrumentation for Brain Organoids

Patel,

Shetty,

Acha

et al. 2024

Adv Healthcare Materials

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Brain organoids are three‐dimensional aggregates of self‐organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs), and optical, magnetic, and acoustic techniques, have limitations when applied to 3D organoids, primarily due to their limits with inherently 2D geometry and interfacing. Hence, there is an urgent need to develop new instrumentation that is compatible with live cell culture techniques and with scalable 3D formats of relevance to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid‐machine interfaces. Specifically, the article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast‐scan optical techniques, buckling and self‐folding microelectrode arrays, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two‐way information transfer with brain organoids. The article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer.This article is protected by copyright. All rights reserved

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Brain organoids

Cited by 3 publications

References 144 publications

Decoding frontotemporal and cell type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs

Decoding frontotemporal and cell type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs

Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs

Microinstrumentation for Brain Organoids

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