BMI Seminar // Metabolic regulation of adult neural stem cells

Neural stem/progenitor cells (NSPCs) generate new neurons throughout life in distinct regions of the mammalian brain. Adult neurogenesis is important for tissue homeostasis and physiological brain function, and disturbed neurogenesis has been associated with diseases such as major depression and epilepsy. A tight regulation of NSPC quiescence and proliferation is crucial to ensure life-long neurogenesis and prevent exhaustion or uncontrolled growth of the stem cell pool. What regulates this delicate balance is not fully understood. We are interested in how cellular metabolism is influencing NSPC activity and how metabolic programs change between quiescent and proliferating NSPCs and their differentiating progeny. We have shown that de novo lipogenesis is crucial for proper NSPC proliferation and integration and have identified the protein Spot14 as a novel functional marker for the most quiescent NSPC population in vivo^1,2. We have further studied how Spot14 is keeping NSPCs quiescent through the regulation of lipid metabolic pathways. We have exciting data showing that quiescent NSPCs depend on the breakdown of lipids via fatty acid oxidation (FAO), that inhibition of FAO in vitro and in vivo results in altered NSPC behavior and that changing the levels of a single metabolite is sufficient to override quiescence cues³. Taken together, we show an instructive role for fatty acid metabolism in regulating NSPC activity in the adult brain.