Abstract
Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.
Highlights
Adult hippocampal neurogenesis is tightly controlled by neural stem cell (NSC) located in the subgranular zone (SGZ) of the mammalian dentate gyrus that proliferate, differentiate, are maintained, and integrate into the local circuitry throughout life [41,42,43,44,45]
The cycle is divided into three stages: anagen, catagen, and telogen (Figure 4) [84]. This regeneration process relies on hair follicle stem cells (HFSCs) and melanocyte stem cells (MeSCs) in the bulge and hair germ region [85,86,87]
Our results have indicated that coordinated activities of nicotinic acetylcholine receptor (nAChR) and Wnt signaling maintain Lgr5+ stem cell activity and balanced differentiation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. ACh may be involved in regulation of stem cell functions such as proliferation, differentiation, and the establishment of cell–cell interactions [22]. ACh receptors (nAChRs) are involved in the proliferation of mouse embryonic and induced pluripotent stem cells [24,25,26]. This evidence leads us to propose the presence of a cholinergic niche that affects stem cell behavior. Adult NSCs have fundamental properties of self-renewal, relative quiescence, differentiation capacity, and residence within a specific environmental niche similar to other adult somatic stem cells (Figure 3) [28]. I review cholinergic signaling involved in postnatal/adult neurogenesis and how patterns of neuronal activity differentially and/or synergistically modulate downstream signaling in NSCs
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