Cell Cycle Entry of Quiescent Neural Stem Cells Decreases Early in the Young Adult Mouse Ventricular-Subventricular Zone But is Stimulated after Injury or Addition of Syndecan-1

Abstract

Neural stem cells (NSCs) from the adult mouse ventricular-subventricular zone (V-SVZ) are contained in cell populations expressing the carbohydrate LeX, and exhibit either characteristics of quiescent NSCs (qNSCs: LeXbright) or of actively dividing NSCs (aNSCs: LeX+EGFR+) based on the absence or the presence of EGF-receptor, respectively. The balance between quiescence and proliferation is central for the long-term NSC maintenance. Using the FUCCI-Cdt1 transgenic mice to mark cells in G0/G1 phase of the cell cycle by red fluorescence, we identified a subpopulation of primed qNSCs. The capacity of primed qNSCs to re-enter the cell cycle decreased with age but was stimulated after radio-induced V-SVZ injury. Furthermore, the addition of recombinant Syndecan-1, a Heparan Sulfate Proteoglycan, both increased proliferation of aNSCs and hastened the division of primed qNSCs. Overall, targeting SDC1 might provide the means to control the proliferation of NSCs and to counteract the neurogenesis decline during aging.