Regulation of metabolism during development is essential for cell expansion and tissue growth. Bioenergetic programs are known to be altered in neurodevelopmental disorders. Yet, we have limited understanding of the mechanistic regulation of and metabolic requirements for brain development. This gap in knowledge is particularly pronounced for the increased cellular heterogeneity and tissue complexity of the human brain. To explore the relationship between metabolism and cell fate decisions, we use cortical organoids and rodent cortex transplant models paired with gene editing tools, single cell transcriptomics, metabolomics and functional approaches to determine the metabolic programs used by discrete, temporally-developing human cortical cell types.
