Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection [expression array]

The human cerebral cortex possess 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 pluripotency 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 report 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 the organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying new candidate receptors and therapeutic compounds that can mitigate its desructive actions. Human cortical organoids were lysed in QIAzol reagents and RNA was extracted following manufacturer's instructions (miRNeasy Micro Kit, Qiagen). Cerebral organoids derived from H9 were collected with 3 replicates (3 independent experiments, 12 samples total) at W5, W8, W11, and W14 and RNA samples were sent to the UCLA Neuroscience Genomic Core. RNA integrity was cofirmed with the Agilent 2100 bioanalyzer (RIN > 8) and samples were hybridized to the HumanHT 12v4.0.