(138e) Human Cerebral Organoids As Models for Neurodevelopmental Disorders and Test-Beds for Therapeutic Strategies

Human cerebral organoids are microtissues derived from pluripotent stem cells with cell diversity and multicellular architectures reminiscent of native brain. These systems hold significant promise in revealing natural and disease mechanisms in neurodevelopment, as well as provide a system to test or screen for therapeutic agents. Here we demonstrate that human cerebral organoids are a useful tool to study neurodevelopmental disorders, in particular Angelman Syndrome and Autism Spectrum Disorder. We focus on the gene UBE3A that is important in both diseases, and show that organoids recapitulate many of the key molecular and cellular features of UBE3A biology found in prior mouse models of Angelman Syndrome, strongly suggesting the validity and utility of this human model system. We also identify striking spatial and temporal differences between UBE3A expression in human and mouse systems that may indicate an important therapeutic time window.