Lysosomes and signaling pathways for maintenance of quiescence in adult neural stem cells

Quiescence is a cellular strategy for maintaining somatic stem cells in a specific niche in a low metabolic state without senescence for a long period of time. During development, neural stem cells (NSCs) actively proliferate and self‐renew, and their progeny differentiate into both neurons and glial cells to form mature brain tissues. On the other hand, most NSCs in the adult brain are quiescent and arrested in G0/G1 phase of the cell cycle. Quiescence is essential in order to avoid the precocious exhaustion of NSCs, ensuring a sustainable source of available stem cells in the brain throughout the lifespan. After receiving activation signals, quiescent NSCs reenter the cell cycle and generate new neurons. This switching between quiescence and proliferation is tightly regulated by diverse signaling pathways. Recent studies suggest significant involvement of cellular proteostasis (homeostasis of the proteome) in the quiescent state of NSCs. Proteostasis is the result of integrated regulation of protein synthesis, folding, and degradation. In this review, we discuss regulation of quiescence by multiple signaling pathways, especially bone morphogenetic protein and Notch signaling, and focus on the functional involvement of the lysosome, an organelle governing cellular degradation, in quiescence of adult NSCs.