Using organoids to study human brain development and evolution

Chan, Wai Kit; Fetit, Rana; Griffiths, Rosie; Marshall, Helen; Mason, John O.; Price, David J.

doi:10.1002/dneu.22819

Cited by 5 publications

(6 citation statements)

References 112 publications

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“…As it is becoming evident that the phenotype of microglia is dependent on the CNS environment, co-culture with astrocytes and/or neurons and 3D culture systems have been shown to further induce the maturation of microglia. Cerebral organoids recapitulate many structural, developmental, and functional features of the human brain, including cytoarchitecture, cell diversity, and transcriptional profile (Chan et al 2021;Chiaradia and Lancaster 2020;Qian et al 2019;Sidhaye and Knoblich 2021). The generation of cerebral organoids can be divided in two categories: non-patterned or patterned.…”

Section: Description Of the Modelsmentioning

confidence: 99%

Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses

et al. 2022

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HIV persistence in the CNS despite antiretroviral therapy may cause neurological disorders and poses a critical challenge for HIV cure. Understanding the pathobiology of HIV-infected microglia, the main viral CNS reservoir, is imperative. Here, we provide a comprehensive comparison of human microglial culture models: cultured primary microglia (pMG), microglial cell lines, monocyte-derived microglia (MDMi), stem cell–derived microglia (iPSC-MG), and microglia grown in 3D cerebral organoids (oMG) as potential model systems to advance HIV research on microglia. Functional characterization revealed phagocytic capabilities and responsiveness to LPS across all models. Microglial transcriptome profiles of uncultured pMG showed the highest similarity to cultured pMG and oMG, followed by iPSC-MG and then MDMi. Direct comparison of HIV infection showed a striking difference, with high levels of viral replication in cultured pMG and MDMi and relatively low levels in oMG resembling HIV infection observed in post-mortem biopsies, while the SV40 and HMC3 cell lines did not support HIV infection. Altogether, based on transcriptional similarities to uncultured pMG and susceptibility to HIV infection, MDMi may serve as a first screening tool, whereas oMG, cultured pMG, and iPSC-MG provide more representative microglial culture models for HIV research. The use of current human microglial cell lines (SV40, HMC3) is not recommended.

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Section: Description Of the Modelsmentioning

confidence: 99%

Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses

et al. 2022

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“…11) Critically evaluate the use of rodent models in understanding early cortical development in humans (Luhmann and Fukuda, 2020) and whether rodents fulfill criteria to study preclinical manifestations of human diseases (Al Dahhan et al, 2019). 12) Organoids may become most valuable models for early cortical development in humans (Trujillo et al, 2019;Chan et al, 2021). However, it needs to be studied whether important cortical circuits present in pre-and neonatal human cortex are also present in organoids (e.g., the fetal subplate circuits Kostovic, 2020;Kostovic et al, 2021).…”

Section: The Open Questions and Future Tasksmentioning

confidence: 99%

“…Organoids may become most valuable models for early cortical development in humans (Trujillo et al, 2019 ; Chan et al, 2021 ). However, it needs to be studied whether important cortical circuits present in pre- and neonatal human cortex are also present in organoids (e.g., the fetal subplate circuits Kostovic, 2020 ; Kostovic et al, 2021 ).…”

Section: The Open Questions and Future Tasksmentioning

confidence: 99%

Neurophysiology of the Developing Cerebral Cortex: What We Have Learned and What We Need to Know

Luhmann

2022

Front. Cell. Neurosci.

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This review article aims to give a brief summary on the novel technologies, the challenges, our current understanding, and the open questions in the field of the neurophysiology of the developing cerebral cortex in rodents. In the past, in vitro electrophysiological and calcium imaging studies on single neurons provided important insights into the function of cellular and subcellular mechanism during early postnatal development. In the past decade, neuronal activity in large cortical networks was recorded in pre- and neonatal rodents in vivo by the use of novel high-density multi-electrode arrays and genetically encoded calcium indicators. These studies demonstrated a surprisingly rich repertoire of spontaneous cortical and subcortical activity patterns, which are currently not completely understood in their functional roles in early development and their impact on cortical maturation. Technological progress in targeted genetic manipulations, optogenetics, and chemogenetics now allow the experimental manipulation of specific neuronal cell types to elucidate the function of early (transient) cortical circuits and their role in the generation of spontaneous and sensory evoked cortical activity patterns. Large-scale interactions between different cortical areas and subcortical regions, characterization of developmental shifts from synchronized to desynchronized activity patterns, identification of transient circuits and hub neurons, role of electrical activity in the control of glial cell differentiation and function are future key tasks to gain further insights into the neurophysiology of the developing cerebral cortex.

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“…This has led to discoveries using organoids to model fetal toxin exposure (Prince et al, 2019 ; Arzua et al, 2020 ) and developmental disorders (Gomes et al, 2020 ). In a novel application of the technology, organoids are being generated from across several species, leading to discoveries about how brain development has changed over evolution (Kanton et al, 2019 ; Benito-Kwiecinski et al, 2021 ; Chan et al, 2021 ). Additionally, protocols have recently been developed to generate human neural crest cells and their derivatives.…”

Section: Complementing and Building On Animal Models With Human Stem Cell Modelsmentioning

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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Using organoids to study human brain development and evolution

Cited by 5 publications

References 112 publications

Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses

Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses

Neurophysiology of the Developing Cerebral Cortex: What We Have Learned and What We Need to Know

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

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