Multi-omics data (phospholipidomic, metabolomic and transcriptomic data) of postnatal microglia

Microglia undergo morphological and functional changes during development, yet little is known about the metabolic programs that shape microglial development. Here, using multi-omics profiling, we generate a landscape of membrane phospholipids and cellular metabolites across microglial development. We reveal sequential shifts in microglial metabolome and phospholipidome during development and uncover critical metabolic features of microglia at early postnatal stages. Distinct from adult microglia utilizing glutamine in the absence of glucose, early postnatal microglia exhibit high uptake and demands for glutamine. Blocking glutaminolysis significantly suppresses early postnatal microglial proliferation and phagocytosis in vivo and in vitro. Isotope tracing demonstrates that glutamine is preferentially fluxed to aspartate, and inhibiting aspartate conversion attenuates microglial proliferation but not phagocytosis, suggesting glutamine fuels into divergent metabolic pathways to support distinct microglial functions. Our study reveals developmentally-regulated metabolic features of microglia and highlights glutamine metabolism as a key player in shaping early microglia.