Using human cortical organoids to understand the impact of glucose metabolism on progenitor developmental trajectories

Dysregulation of glucose metabolism occurs in neurodevelopmental disorders, yet the specific consequences on the molecular regulation of cellular development and tissue formation during neurogenesis are not fully understood. Since the molecular characterization of the developing human brain is impossible and it is inaccessible to longitudinally study onset of neurodevelopmental disorders, we rely on alternative model systems. Human Cortical Organoids (HCOs) are self-organizing three-dimensional cultures, derived from human pluripotent stem cells, that model features of the developing human cerebral cortex. HCOs serve as robust in vitro cellular models that allow us to observe cell division and differentiation programs in human neural cells. Though HCOs are the most-advanced human cellular models available, they suffer limitations such as the overexpression of genes associated with metabolism compared to primary samples. In this study, we intend to determine how our model differs metabolically from primary tissue and overcome the challenges related to modeling metabolism in HCOs by creating more endogenous culture conditions. Here we present preliminary results, comparing gene expression and cell type proportions at relevant timepoints through qPCR and Immunohistochemistry, respectively.