QB3 Webinar: Arnold Kriegstein, UCSF. “Transforming Genomic Insights From Human Brain Development Into Life-Changing Therapies”

The human cerebral cortex is more than three times expanded compared to our closest non-human primate relatives. The cortex emerges from an initially pseudostratified neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. A number of subtypes of radial glia have been identified, and single cell RNA sequencing has enabled the construction of a multi-omic molecular atlas of the human neocortex across different developmental stages at single-cell resolution. The results illuminate molecular and cellular dynamics of the developing human neocortex, including cellular composition, spatial organization, intercellular signaling, gene regulatory networks, lineage potential, and disease susceptibilities, highlighting novel progenitor cell lineages and shedding light on mechanisms of glioblastoma and neuropsychiatric disorders. Importantly, the data provide a roadmap for the derivation of specific neural cell types from pluripotent stem cells. This information has been used to create inhibitory interneurons that are now being tested in patients with medically-resistant temporal lobe epilepsy. The results are encouraging, and a pivotal clinical trial is planned that could lead to a novel approved cell-based therapy for epilepsy.