Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(12), P. 1496 - 1508

Published: Nov. 2, 2020

Language: Английский

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Human organoids in basic research and clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 24, 2022

Abstract Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult (AdSCs) derived healthy individuals patients that recapitulate the cellular heterogeneity, structure, and functions of organs. The advent 3D organoid systems is now possible to allow remarkably detailed observation cell morphogens, maintenance differentiation resemble primary tissues, enhancing potential study both physiology developmental stage. As they similar their original organs carry genetic information, organoids patient hold great promise for biomedical research preclinical drug testing currently used personalized, regenerative medicine, gene repair transplantation therapy. In recent decades, researchers have succeeded generating various types mimicking vivo Herein, we provide an update on current technologies brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized multi-lineage organoids, discuss differences between PSC- AdSC-derived summarize applications cell-derived laboratory clinic, outline challenges application which would deepen understanding mechanisms development enhance further utility basic clinical studies.

Language: Английский

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Molecular landscapes of human hippocampal immature neurons across lifespan

Nature, Journal Year: 2022, Volume and Issue: 607(7919), P. 527 - 533

Published: July 6, 2022

Language: Английский

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Human brain organogenesis: Toward a cellular understanding of development and disease

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 42 - 61

Published: Nov. 11, 2021

Language: Английский

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Human cerebral organoids — a new tool for clinical neurology research

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(11), P. 661 - 680

Published: Oct. 17, 2022

Language: Английский

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Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology

Stem Cell Reports, Journal Year: 2021, Volume and Issue: 16(8), P. 1923 - 1937

Published: July 22, 2021

Microglia play critical roles in brain development, homeostasis, and disease. animal models cannot accurately model human microglia due to notable transcriptomic functional differences between other microglia. Incorporating pluripotent stem cell (hPSC)-derived into organoids provides unprecedented opportunities study However, an optimized method that integrates appropriate amounts of at a proper time point, resembling vivo is still lacking. Here, we report new region-specific, microglia-containing organoid by co-culturing hPSC-derived primitive neural progenitor cells macrophage progenitors. In the organoids, number can be controlled, exhibit phagocytic activity synaptic pruning function. Furthermore, respond Zika virus infection organoids. Our findings establish will serve microglial function variety neurological disorders.

Language: Английский

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Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3770 - 3788.e27

Published: Sept. 1, 2022

Language: Английский

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Challenges of Organoid Research

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 23 - 39

Published: Jan. 5, 2022

Organoids are 3D cell culture systems derived from human pluripotent stem cells that contain tissue resident types and reflect features of early organization. Neural organoids a particularly innovative scientific advance given the lack accessibility developing brain intractability neurological diseases. have become an invaluable approach to model development not well reflected in animal models. also hold promise for study atypical cellular, molecular, genetic underscore Additionally, may provide platform testing therapeutics potential source replacement approaches injury or disease. Despite promising organoids, their broad utility is tempered by variety limitations yet be overcome, including high-fidelity types, limited maturation, physiology, arealization, limit reliability certain applications.

Language: Английский

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Functional neuronal circuitry and oscillatory dynamics in human brain organoids

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 29, 2022

Human brain organoids replicate much of the cellular diversity and developmental anatomy human brain. However, physiology neuronal circuits within remains under-explored. With high-density CMOS microelectrode arrays shank electrodes, we captured spontaneous extracellular activity from derived induced pluripotent stem cells. We inferred functional connectivity spike timing, revealing a large number weak connections skeleton significantly fewer strong connections. A benzodiazepine increased uniformity firing patterns decreased relative fraction weakly connected edges. Our analysis local field potential demonstrate that contain assemblies sufficient size to co-activate generate potentials their collective transmembrane currents phase-lock spiking activity. These results point for study neuropsychiatric diseases, drug action, effects external stimuli upon networks.

Language: Английский

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Single-cell brain organoid screening identifies developmental defects in autism

Nature, Journal Year: 2023, Volume and Issue: 621(7978), P. 373 - 380

Published: Sept. 13, 2023

Abstract The development of the human brain involves unique processes (not observed in many other species) that can contribute to neurodevelopmental disorders 1–4 . Cerebral organoids enable study a context. We have developed CRISPR–human organoids–single-cell RNA sequencing (CHOOSE) system, which uses verified pairs guide RNAs, inducible CRISPR–Cas9-based genetic disruption and single-cell transcriptomics for pooled loss-of-function screening mosaic organoids. Here we show perturbation 36 high-risk autism spectrum disorder genes related transcriptional regulation uncovers their effects on cell fate determination. find dorsal intermediate progenitors, ventral progenitors upper-layer excitatory neurons are among most vulnerable types. construct developmental gene regulatory network cerebral from transcriptomes chromatin modalities identify disorder-associated perturbation-enriched modules. Perturbing members BRG1/BRM-associated factor (BAF) remodelling complex leads enrichment telencephalon progenitors. Specifically, mutating BAF subunit ARID1B affects transition oligodendrocyte interneuron precursor cells, phenotype confirmed patient-specific induced pluripotent stem cell-derived Our paves way high-throughput phenotypic characterization disease susceptibility organoid models with state, molecular pathway readouts.

Language: Английский

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