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  • Neural stem cells in adult

    2018-10-20

    Neural stem cells in adult rodents are mainly restricted to the niches at the subventricular zone (SVZ) in the lateral ventricles and the subgranular zone (SGZ) in the hippocampal dentate gyrus (Doetsch et al., 1999; Palmer et al., 1997; Reynolds and phospholipase inhibitor Weiss, 1992; Richards et al., 1992). In the adult SVZ, type phospholipase inhibitor express glial markers, have astrocyte characteristics, bundles of intermediate filaments and multiple processes (Doetsch et al., 1999; Peters et al., 1991), and generate neuroblasts (type A cells, neuronal precursors) through a highly proliferative transit amplifying population (type C cells) (Doetsch et al., 1999; Kriegstein and Alvarez-Buylla, 2009). The cell bodies of type B astrocytes are generally located under the ependymal layer of the lateral ventricles, have short processes that extend through it, with small apical endings on the ventricle, in addition to frequently tangentially oriented long basal processes with specialized end feet on blood vessels (Kriegstein and Alvarez-Buylla, 2009; Mirzadeh et al., 2008). Thus, adult SVZ B cells, similarly to the radial glia (RG) during development, retain an apical–basal polarity and are part of the ventricular epithelium (Kriegstein and Alvarez-Buylla, 2009). In fact, although the radial glia disappears postnatally by transformation into parenchymal astrocytes, some radial glial cells persist within the adult SVZ hidden among astrocytes of the glial tubes. This modified radial glia belongs to the astroglial lineage (type B cells) and maintains self-renewal potential and pluripotency, the two stem cell characteristics (Bonfanti and Peretto, 2007; Gubert et al., 2009; Sundholm-Peters et al., 2004). It is well documented the migration of adult neuroblasts in a pathway known as rostral migratory stream (RMS), in longitudinal clusters from their SVZ niche towards the olfactory bulb (OB), where dying neurons should be replaced (Doetsch et al., 1999; Doetsch and Alvarez-Buylla, 1996; Lois and Alvarez-Buylla, 1994; Lois et al., 1996). In addition, migration of cells from SVZ towards non-olfactory bulb regions in the adult has been reported on several disease or injury models (Arvidsson et al., 2002; Cantarella et al., 2008; Nakatomi et al., 2002; Thored et al., 2006). Surgical RMS disruption led to migration of BdrU+PSA-NCAM+ cells from the SVZ into the anterior olfactory nucleus, the frontal cortex and the striatum (Alonso et al., 1999; Jankovski et al., 1998). In addition, in response to an induced brain tumor, the migration of endogenous neuroblasts towards the lesion site could be followed in vivo by MRI (Elvira et al., 2012). Although DCX+ neuroblasts are thought to be the major migratory SVZ cells, type C cells might migrate as well (Aguirre and Gallo, 2004). Many of the migration experiments have been done using BrdU-labeled cells, where some, but not all the labeled cells were neuroblasts (Arvidsson et al., 2002; Cantarella et al., 2008; Nakatomi et al., 2002; Thored et al., 2006; Gotts and Chesselet, 2005; Sundholm-Peters et al., 2005). Indeed, several reports suggest that other precursor cells from the SVZ are able to migrate towards a brain lesion site. For instance, on transgenic mice expressing a nestin driven green fluorescent protein (GFP), in response to a glioblastoma, the GFP+ cells surrounding the brain tumor were actively dividing (Ki67+), mushashi+, glial precursors (NG2+), GFAP+, PSA-NCAM+ or DCX+. These phenotypes at the lesion site are compatible with the migration of committed and non-committed precursors (Glass et al., 2005). Time-lapse experiments showed that among the nestin-eGFP+ cells in the SVZ, there were type C cells, GFAP+ cells, neuroblasts, ependymal cells and microglia, where a high percentage of motile nestin-eGFP+ cells were DCX− (Nam et al., 2007). Taken together, these data suggest that DCX+ neuroblasts do not represent the only motile SVZ-derived cells in the postnatal mouse brain. In cortical injuries, NG2+ cells, Nestin+ GFAP+ cells or SVZ cells able to differentiate into glia were identified in the vicinity of the lesion site at different time points (Glass et al., 2005; Goings et al., 2004; Picard-Riera et al., 2002; Holmin et al., 1997).