Maternal lipids prime quiescent neural stem cells to reactivate in response to dietary nutrients

Abstract

Stem cell quiescence--a state of mitotic and metabolic dormancy--is essential for tissue homeostasis and for coordinating growth with nutrient availability. Switching between quiescence and proliferation is controlled through stem cell intrinsic and extrinsic cues, with diet being key as diet provides macro-and micro-nutrients needed for synthesizing new membrane, protein, and nucleic acids. Yet, it remains unclear what nutrients control the stem cell switch and whether nutrient sources other than diet are required. Here, we report that lipids deposited maternally in the embryo regulate reactivation of Drosophila neural stem cells (neuroblasts) from quiescence. This maternal nutrient source is in addition to the known dietary amino acids required during larval feeding1. Females fed reduced lipid diets or carrying mutations in genes essential for lipid deposition and metabolism produce larvae with fewer stored lipids in neural tissues. Reduced neural lipid stores result in delayed glial growth and neuroblast reactivation due to the inability of neuroblasts to activate PI3-kinase signaling in response to diet-induced expression of insulin-like peptides. Thus, neuroblasts rely on two nutrient sources, maternal and dietary, raising the possibility that quiescent stem cells in general access and utilize stored and acquired nutrients coordinately to switch between stem cell states.