학술논문

Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection.
Document Type
article
Source
Cell reports. 21(2)
Subject
Cerebral Cortex
Neurons
Organoids
Cell Line
Humans
Receptor Protein-Tyrosine Kinases
Anti-Retroviral Agents
Drug Evaluation
Preclinical
STAT3 Transcription Factor
Embryonic Stem Cells
Primary Cell Culture
Zika Virus
c-Mer Tyrosine Kinase
Zika virus
cerebral cortex
differentiation
embryonic stem cell
human brain
neural development
neural stem cell
neurogenesis
organoid
Regenerative Medicine
Neurosciences
Stem Cell Research - Nonembryonic - Human
Stem Cell Research - Embryonic - Human
Stem Cell Research
Stem Cell Research - Induced Pluripotent Stem Cell
Stem Cell Research - Induced Pluripotent Stem Cell - Human
Brain Disorders
Neurological
Good Health and Well Being
Biochemistry and Cell Biology
Medical Physiology
Language
Abstract
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.