Glial cells in non-germinal territories: insights into their stem/progenitor properties in the intact and injured nervous tissue.

In the adult murine central nervous system (CNS), the germinal astroglia residing in the subependymal zone of the lateral ventricles and in the subgranular layer of the hippocampal dentate gyrus behaves as neural stem cells actively undergoing neurogenesis and gliogenesis. Although neurogenesis does not normally occur outside the germinal niches, two types of parenchymal glial cells, namely astrocytes and NG2-expressing cells, display distinct progenitor activities in the intact brain or upon injury. Importantly, in defined experimental conditions both cell types reveal the potential to behave as multipotent stem cells suggesting that the mature CNS parenchyma may retain a latent stem cell potential, normally inhibited in vivo that, if properly evoked, might be exploited in situ for endogenous cell replacement following injury. In this review we scrutinise recent studies focussing on (i) the molecular and functional relationships between precursors in germinal niches and non-germinal areas; (ii) the ability of adult parenchymal glia to undergo lineage transgressions and neurogenesis in the intact brain and upon CNS injury. We also compare evidence for lineage plasticity in astrocytes or NG2+ cells, and discuss possible approaches for the implementation of stem/progenitor cell capabilities in non-germinal glial cells.