Gene expression in classes of adult hippocampal precursor cells defined by ROS content

Regulating the cell cycle entry of neural stem cells (NSCs) is critical for continued adult neurogenesis and is extensively shown to be subject to environmental modulation. Here we demonstrate that pro-proliferative stimulation by physical activity is achieved by activating quiescent hippocampal precursors. Using independent approaches, we show that differential enrichment of endogenous ROS distinguishes this pool of activatable, quiescent cells. Endogenous ROS content clusters Nestin (Nes)-GFP+ precursor cells into heterogeneous cell populations with unique transcriptional identities and significant changes in ROS content precede gene expression changes and neurogenic commitment. A sub-optimal physical activity triggers a ROS surge exclusively in cells with high intracellular ROS content underpinning their recruitment into active growth cycle. These ROS dynamics are independent of mitochondrial function and are driven by the activity of NADPH oxidising enzyme Nox2. While baseline neurogenesis is unaffected, ROS fluctuations and the pro-neurogenic response to physical activity was abolished in Nox2-deficient mice. Overall design: 14 samples in 3 experimental groups with 4/5 replicates per group