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Brain Organoids and the Study of Neurodevelopment

类有机物 人脑 神经科学 生物 表观遗传学 诱导多能干细胞 小头畸形 计算生物学 胚胎干细胞 遗传学 基因
作者
Cleber A. Trujillo,Alysson R. Muotri
出处
期刊:Trends in Molecular Medicine [Elsevier BV]
卷期号:24 (12): 982-990 被引量:115
标识
DOI:10.1016/j.molmed.2018.09.005
摘要

Brain organoids are 3D self-assembled structures that recapitulate crucial molecular and cellular steps of brain development. Protocols exist to create brain organoids in a dish from human pluripotent stem cells derived from patients and healthy individuals. The incorporation of single-cell sequencing, genome editing, and optogenetics could improve the application of brain organoids. Human brain organoids are being used to understand monogenetic and syndromic neurodevelopmental disorders, as well as environmental causes of neurological conditions, such as Zika pathophysiology. Brain organoids are 3D self-assembled structures composed of hundreds of thousands to millions of cells that resemble the cellular organization and transcriptional and epigenetic signature of a developing human brain. Advancements using brain organoids have been made to elucidate the genetic basis of certain neurodevelopmental disorders, such as microcephaly and autism; and to investigate the impact of environmental factors to the brain, such as during Zika virus infection. It remains to be explored how far brain organoids can functionally mature and process external information. An improved brain organoid model might reproduce important aspects of the human brain in a more reproducible and high-throughput fashion. This novel and complementary approach in the neuroscience toolbox opens perspectives to understand the fundamental features of the human neurodevelopment, with implications to personalize therapeutic opportunities for neurological disorders. Brain organoids are 3D self-assembled structures composed of hundreds of thousands to millions of cells that resemble the cellular organization and transcriptional and epigenetic signature of a developing human brain. Advancements using brain organoids have been made to elucidate the genetic basis of certain neurodevelopmental disorders, such as microcephaly and autism; and to investigate the impact of environmental factors to the brain, such as during Zika virus infection. It remains to be explored how far brain organoids can functionally mature and process external information. An improved brain organoid model might reproduce important aspects of the human brain in a more reproducible and high-throughput fashion. This novel and complementary approach in the neuroscience toolbox opens perspectives to understand the fundamental features of the human neurodevelopment, with implications to personalize therapeutic opportunities for neurological disorders. a controlled technique for fusion of organoids from different brain regions to recapitulate the saltatory migration of interneurons in vitro. repetitive and synchronized electrical activity generated from neurons communicating with each other. The activity of a large group of neurons can be registered in an electroencephalogram using sensors to detect variations in the local field potential. imaging technique designed to measure the amount of calcium on isolated cells. In neurosciences, calcium transients in neurons are frequently associated with functionality. CRISPR/Cas system is used to create targeted breaks in the DNA, allowing a custom editing of the genome. Originally, the CRISPR system conferred resistance to prokaryotes by detecting and cutting exogenous DNA elements. In eukaryotes, this system was optimized as a powerful tool for genome editing. a mathematical technique that can be used to determine the optimal set of conditions across many different changeable parameters. method to record electrical brain activity in a noninvasive fashion using electrodes on the scalp of an individual. cells that have the same genetic background, except for an introduced or deleted target gene mutation. Usually, they are genetically engineered to model a specific condition, and the non-mutated cell line is used as a corresponding control. a medical condition where the head circumference is smaller than a typically developing child. cellular response induced by activation of membrane light-sensitive channels. technology used to control cellular activity by expressing genetically encoded light-sensitive channels. a technique frequently used in neuroscience to measure ionic currents and voltage passing across the membrane (action potentials) in individual neurons. cells that are able to differentiate into all three germ layers of an animal embryo. insertion mechanism of genetic material that can self-amplify and integrate into the genome. composed of a nuclease fused with a DNA-binding domain that can be modified to target and cleave specific DNA sequences. a modified rabies virus that allows the labeling of neurons connected through synapsis to reconstruct brain circuitry. uncontrolled presence of material from a different species.
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