Genetic and Epigenetic Regulation of Brain Organoids

Wang, Youwei; Hu, Nan; Li, Xiaohong

doi:10.3389/fcell.2022.948818

Cited by 4 publications

(4 citation statements)

References 43 publications

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“…S4D ). Mixed regional signatures suggest that cells were too immature to be confidently identified -organoids generating less distinguishable cell types than in vivo 51 - or represented lineages shared or migrating between brain regions. At the used morphogen concentrations, only limited expression for posterior hindbrain/spinal cord or neural crest fates was evident at d64.…”

Section: Resultsmentioning

confidence: 99%

Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids

Scuderi,

Kang,

Jourdon

et al. 2024

Preprint

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The repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain. Morphogens crosstalk translated into early patterns of gene expression programs predicting the generation of specific brain lineages. Human iPSC lines from six different genetic backgrounds showed substantial differences in response to morphogens, suggesting that interindividual genomic and epigenomic variations could impact brain lineages formation. Morphogen gradients promise to be a key approach to model the brain in its entirety.

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Section: Resultsmentioning

confidence: 99%

Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids

Scuderi,

Kang,

Jourdon

et al. 2024

Preprint

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“…Brain organoids have also been used to study genetic and epigenetic regulation of the brain, neuronal connectivity, and neuro-immune interactions in healthy and diseased brains [ 60 , 113 ]. These are relevant aspects of migraine pathogenesis that must be considered in the development and use of brain organoids for migraines.…”

Section: Potential and Limitations Of Brain Organoids For Migrainementioning

confidence: 99%

Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

Gazerani

2023

IJMS

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Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways to treat disease. Organoids of the liver, kidney, intestine, lung, and brain have been developed in recent years. Human brain organoids are used for understanding pathogenesis and investigating therapeutic options for neurodevelopmental, neuropsychiatric, neurodegenerative, and neurological disorders. Theoretically, several brain disorders can be modeled with the aid of human brain organoids, and hence the potential exists for understanding migraine pathogenesis and its treatment with the aid of brain organoids. Migraine is considered a brain disorder with neurological and non-neurological abnormalities and symptoms. Both genetic and environmental factors play essential roles in migraine pathogenesis and its clinical manifestations. Several types of migraines are classified, for example, migraines with and without aura, and human brain organoids can be developed from patients with these types of migraines to study genetic factors (e.g., channelopathy in calcium channels) and environmental stressors (e.g., chemical and mechanical). In these models, drug candidates for therapeutic purposes can also be tested. Here, the potential and limitations of human brain organoids for studying migraine pathogenesis and its treatment are communicated to generate motivation and stimulate curiosity for further research. This must, however, be considered alongside the complexity of the concept of brain organoids and the neuroethical aspects of the topic. Interested researchers are invited to join the network for protocol development and testing the hypothesis presented here.

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“…Brain organoids have been shown to be a suitable model for studying human neurodevelopment and have been widely used to answer biological questions. They have allowed researchers to gain better understanding of multiple topics, such as the genetic mechanisms driving human brain evolution [ 23 – 26 ], the effect of pollutants on brain development [ 27 – 29 ], and of the neurotrophic effects of multiple drugs [ 30 – 32 ]. Additionally, human brain organoids have helped to understand the neurological impact that a variety of viruses can have on the brain (reviewed by Depla et al [ 33 ]), including the recent SARS-CoV-2 virus [ 34 – 36 ].…”

Section: Introductionmentioning

confidence: 99%

A beginner’s guide on the use of brain organoids for neuroscientists: a systematic review

et al. 2023

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Background The first human brain organoid protocol was presented in the beginning of the previous decade, and since then, the field witnessed the development of many new brain region-specific models, and subsequent protocol adaptations and modifications. The vast amount of data available on brain organoid technology may be overwhelming for scientists new to the field and consequently decrease its accessibility. Here, we aimed at providing a practical guide for new researchers in the field by systematically reviewing human brain organoid publications. Methods Articles published between 2010 and 2020 were selected and categorised for brain organoid applications. Those describing neurodevelopmental studies or protocols for novel organoid models were further analysed for culture duration of the brain organoids, protocol comparisons of key aspects of organoid generation, and performed functional characterisation assays. We then summarised the approaches taken for different models and analysed the application of small molecules and growth factors used to achieve organoid regionalisation. Finally, we analysed articles for organoid cell type compositions, the reported time points per cell type, and for immunofluorescence markers used to characterise different cell types. Results Calcium imaging and patch clamp analysis were the most frequently used neuronal activity assays in brain organoids. Neural activity was shown in all analysed models, yet network activity was age, model, and assay dependent. Induction of dorsal forebrain organoids was primarily achieved through combined (dual) SMAD and Wnt signalling inhibition. Ventral forebrain organoid induction was performed with dual SMAD and Wnt signalling inhibition, together with additional activation of the Shh pathway. Cerebral organoids and dorsal forebrain model presented the most cell types between days 35 and 60. At 84 days, dorsal forebrain organoids contain astrocytes and potentially oligodendrocytes. Immunofluorescence analysis showed cell type-specific application of non-exclusive markers for multiple cell types. Conclusions We provide an easily accessible overview of human brain organoid cultures, which may help those working with brain organoids to define their choice of model, culture time, functional assay, differentiation, and characterisation strategies.

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Genetic and Epigenetic Regulation of Brain Organoids

Cited by 4 publications

References 43 publications

Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids

Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids

Human Brain Organoids in Migraine Research: Pathogenesis and Drug Development

A beginner’s guide on the use of brain organoids for neuroscientists: a systematic review

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