Abstract
The brain of adult mammals, including humans, contains neural stem cells (NSCs) located within specific niches of which the ventricular-subventricular zone (V-SVZ) is the largest one. Under physiological conditions, NSCs proliferate, self-renew and produce new neurons and glial cells. Several recent studies established that oncogenic mutations in adult NSCs of the V-SVZ are responsible for the emergence of malignant primary brain tumors called glioblastoma. These aggressive tumors contain a small subpopulation of cells, the glioblastoma stem cells (GSCs), that are endowed with proliferative and self-renewal abilities like NSCs from which they may arise. GSCs are thus considered as the cells that initiate and sustain tumor growth and, because of their resistance to current treatments, provoke tumor relapse. A growing body of studies supports that Ca2+ signaling controls a variety of processes in NSCs and GSCs. Ca2+ is a ubiquitous second messenger whose fluctuations of its intracellular concentrations are handled by channels, pumps, exchangers, and Ca2+ binding proteins. The concerted action of the Ca2+ toolkit components encodes specific Ca2+ signals with defined spatio-temporal characteristics that determine the cellular responses. In this review, after a general overview of the adult brain NSCs and GSCs, we focus on the multiple roles of the Ca2+ toolkit in NSCs and discuss how GSCs hijack these mechanisms to promote tumor growth. Extensive knowledge of the role of the Ca2+ toolkit in the management of essential functions in healthy and pathological stem cells of the adult brain should help to identify promising targets for clinical applications.
Highlights
In the brain of adult mammals, including humans, neural stem cells (NSCs) reside within two major regions: the ventricularsubventricular zone (V-SVZ, called the subependymal zone or subventricular zone) lining the lateral brain ventricles and the subgranular zone of the dentate gyrus in the hippocampus
The P2X7R subtype that has been detected in ependymal (E) is expressed in transient amplifying progenitors (C cells) where it plays a dual role: in the absence of the ligand, P2X7R functions as a scavenger receptor involved in phagocytosis and following its activation by adenosine triphosphate (ATP), the P2X7R reduces proliferation of C cells (Genzen et al, 2009; Messemer et al, 2013; Leeson et al, 2018)
Our review highlights a central role of Ca2+ in both NSCs and glioblastoma stem cell (GSC), which is correlated to prominence of Ca2+-related transcripts in both cell types
Summary
In the brain of adult mammals, including humans, neural stem cells (NSCs) reside within two major regions: the ventricularsubventricular zone (V-SVZ, called the subependymal zone or subventricular zone) lining the lateral brain ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The existence of migrating neuroblasts along a RMS and incorporation of new neurons in the human olfactory bulb seems nearly extinct there are conflicting results providing evidence of a maintenance neurogenic activity in the V-SVZ of the adult human brain (Curtis et al, 2007; Sanai et al, 2011; Wang et al, 2011; Paredes et al, 2016).
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