![]() ![]() ( C) High-magnification (HM) confocal images of TAM-induced td-Tom recombination (red), Ki67 (green), doublecortin (DCX white), and DAPI (blue) immunostaining at P38 in the DG. ( B) LM confocal images of TAM-induced td-Tom recombination (red), Ki67 (green), and DAPI (blue) immunostaining at P38 in the DG. ( A) Generation of MPC1 cKO-tdTom and MPC1 WT-tdTom mice and experimental timeline of tamoxifen (TAM) injections (green arrows) and data analysis (black arrow). n = 6 coverslips from three independent experiments (one-way ANOVA followed by post hoc test). ( I) Quantification of pH3 + in control or UK5099-treated quiescent NSPCs. ( H) Experimental outline and images of pH3 and 4′,6-diamidino-2-phenylindole (DAPI) immunostaining in quiescent NSPCs treated with UK5099. *** P < 0.001, n = 3 biological replicates (one-way ANOVA followed by post hoc test). MPC1 protein levels were normalized to mitochondrial HSP70 levels and expressed as fold change to proliferative NSPCs. ( G) Representative Western blots of MPC1 (12 kDa), MPC2 (14 kDa), and HSP70 (70KDa) in proliferative, quiescent, and ex-quiescent NSPCs. ** P < 0.01, n = 3 biological replicates (one-way ANOVA followed by post hoc test). ( F) Relative mRNA expression of Mpc1 in proliferative, quiescent, and ex-quiescent NSPCs. ( E) Experimental outline of quiescence induction. ( D) Quantification of MPC1 in Nestin-GFP–positive quiescent and proliferative NSPCs. ( C) Low-magnification (LM) and high-magnification confocal images of GFP (green), MPC1 (red), and Ki67 (white) immunostaining in DG of Nestin-GFP reporter mice. ( B) Violin plots of Mpc1 expression in quiescent NSPCs, activated NSPCs and intermediate progenitor cells, data queried from ( 27). NSPCs are shown as radial glia (RG) and radial glia–like cells (RGL). ( A) t-distributed stochastic neighbor embedding visualization of Mpc1 expression in the DG of adult mice ( /dentate). These findings highlight the importance of metabolism for NSPC regulation and identify an important pathway through which mitochondrial pyruvate import controls NSPC quiescence and activation. Furthermore, genetic Mpc1 ablation in vitro and in vivo also activates NSPCs, which differentiate into mature neurons, leading to overall increased hippocampal neurogenesis in adult and aged mice. Pharmacological MPC inhibition increases aspartate and triggers NSPC activation. We show that quiescent NSPCs have an active mitochondrial metabolism and express high levels of MPC. Despite its metabolic key function, the role of MPC in NSPCs has not been addressed. ![]() MPC transports pyruvate into mitochondria, linking cytosolic glycolysis to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. We here show that the mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part in this process. However, its role in the transition from quiescence to proliferation is not fully understood. Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. ![]()
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