Cell Reports
Volume 21, Issue 2, 10 October 2017, Pages 517-532
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Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection

https://doi.org/10.1016/j.celrep.2017.09.047Get rights and content
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Highlights

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    Simple yet efficient and reproducible methods for generating human brain organoids

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    STAT3 signaling increases bRG cell formation, corticogenesis, and astrogliogenesis

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    Identification of TIM1, TYRO3, and MER as candidate ZIKV receptors in the fetal brain

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    Identification of multiple compounds capable of mitigating ZIKV-induced cytopathy

Summary

The human cerebral cortex possesses distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotent stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain. Here, we describe optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. Neurons within the organoids are functional and exhibit network-like activities. We further demonstrate the utility of this organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying more susceptibility receptors and therapeutic compounds that can mitigate its destructive actions.

Keywords

neurogenesis
neural stem cell
embryonic stem cell
organoid
differentiation
neural development
cerebral cortex
Zika virus
human brain

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