The Critical Balance Between Quiescence and Reactivation of Neural Stem Cells

Abstract

Neural stem cells (NSC) are multipotent, self-renewing cells that give rise to all neural cell types within the central nervous system. During adulthood, most NSCs exist in a quiescent state which can be reactivated in response to metabolic and signalling changes, allowing for long-term continuous neurogenesis and response to injury. Ensuring a critical balance between quiescence and reactivation is required to maintain the limited NSC reservoir and neural replenishment throughout lifetime. The precise mechanisms and signalling pathways behind this balance are at the focus of current research. In this review, we highlight and discuss recent studies using Drosophila, mammalian and zebrafish models contributing to the understanding of molecular mechanisms underlying quiescence and reactivation of NSCs.

Keywords: damage repair; neural stem cells; quiescence; reactivation.

Figure 1

Several main features of quiescent and active NSCs. Alterations in metabolism, cell adhesion, Extracellular matrix (ECM), cilia/ protrusion, autophagy/ lysosomes, epigenetics regulation, SUMOylation, poly-A RNA nuclear accumulation and several ligand-receptors are depicted [6,12,17,27,28,29,30,31,32]. qNSC: quiescent NSC; aNSC: active NSC. Adapted from [33]. Created in BioRender [34].

Figure 2

Key signalling pathways and processes involved in quiescence and reactivation of NSCs discussed in this review, and their interactions identified in Drosophila, mammalian or zebrafish models. Colour-coded boxes indicate of which model the data has been derived from. Arrow: activation; Bar: repression.