GSE97919
Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection [RNA-seq]
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. Overall design: Human cerebral organoids were differenitated from H9. For ZIKV analyses, ~ 8W-old cortical organoids with mock or ZIKV infection (~MOI 1.67) after 3 days and 5 days of post infection were collected with 3 biological replicates (6 samples total). RNA samples were sent to the UCLA Clinical Microarray Core (CMC) and RNA integrity was confirmed with the Agilent 2100 bioanalyzer. The cDNA libraries were generated using the KAPA stranded mRNA-Seq kits (KAPA Biosystems) and sequenced by Illumina HiSeq 3000, yielding between 27 and 101 million reads per sample.