Quiescent Adult Neural Stem Cells: Developmental Origin and Regulatory Mechanisms

Abstract

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small in number and restricted to the sub-ventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, and the olfactory epithelium, is a gift of evolution for the adaptive brain function which requires persistent plastic changes of these regions. It is known that most adult NSCs are latent, showing long cell cycles. In the past decade, the concept of quiescent NSCs (qNSCs) has been widely accepted by researchers in the field, and great progress has been made in the biology of qNSCs. Although the spontaneous neuronal regeneration derived from adult NSCs is not significant, understanding how the behaviors of qNSCs are regulated sheds light on stimulating endogenous NSC-based neuronal regeneration. In this review, we mainly focus on the recent progress of the developmental origin and regulatory mechanisms that maintain qNSCs under normal conditions, and that mobilize qNSCs under pathological conditions, hoping to give some insights for future study.

Keywords: Injury; Neural stem cell; Neuronal regeneration; Quiescent.

Fig. 1

Outline of the two models for the developmental origin of adult NSCs. A The traditional view holds that adult NSCs appear postnatally. B The set-aside model holds that a subgroup of embryonic NSCs becomes quiescent, forming adult NSCs in the early stage.

Fig. 2

Potential markers for qNSCs, aNSCs, neuroblasts, immature neurons, and mature neurons.

Fig. 3

Outline of qNSCs and aNSCs in their niches under normal (A) and injured conditions (B). Both qNSCs and aNSCs can be mobilized by injury-associated factors released by immune cells and dying neuronal cells.