Abstract
Adult neural stem cells (aNSCs) are the source for the continuous production of new neurons throughout life. This so-called adult neurogenesis has been extensively studied; the intermediate cellular stages are well documented. Recent discoveries have raised new controversies in the field, such as the notion that progenitor cells hold similar self-renewal potential as stem cells, or whether different types of aNSCs exist. Here, we discuss evidence for heterogeneity of aNSCs, including short-term and long-term self-renewing aNSCs, regional and temporal differences in aNSC function, and single cell transcriptomics. Reviewing various genetic mouse models used for targeting aNSCs and lineage tracing, we consider potential lineage relationships between Ascl1-, Gli1-, and Nestin-targeted aNSCs. We present a multidimensional model of adult neurogenesis that incorporates recent findings and conclude that stemness is a phenotype, a state of properties that can change with time, rather than a cell property, which is static and immutable. We argue that singular aNSCs do not exist.
Highlights
Adut Neurogenic Niches Adult neural stem cells (aNSCs) exist in three discrete areas, so-called ‘niches’, of the adult mammalian brain: in the subgranular zone (SGZ) of the hippocampus, in the subventricular zone (SVZ) of the lateral ventricles, and in the walls of the 3rd ventricle (3V) surrounded by the hypothalamus [1–4], which we name here as the hypothalamic ventricular zone (HVZ)
The adult HVZ niche was observed in mice, rats, sheep [5], lemurs, and humans as containing aNSC marker-expressing ependymocytes called tanycytes [6–8]
The origin of aNSCs of the adult HVZ is traced to Sonic Hedgehog (Shh)-expressing progenitors from the embryonic floorplate [38,39]
Summary
2. Adut Neurogenic Niches aNSCs exist in three discrete areas, so-called ‘niches’, of the adult mammalian brain: in the subgranular zone (SGZ) of the hippocampus, in the subventricular zone (SVZ) of the lateral ventricles, and in the walls of the 3rd ventricle (3V) surrounded by the hypothalamus [1–4], which we name here as the hypothalamic ventricular zone (HVZ). In a comparative study of ovine, mouse, and human hypothalamus, Battalier et al, observed immature doublecortin (DCX)-positive and mature, Human Neuronal Protein C and D (HuC/D)-positive neurons occurring in hypothalamic nuclei [5] This neurogenic potential of tanycytes in adult mice is further supported by their expression of the neurogenesis related protein doublecortin-like (DCL) [13], which was shown to co-localize with DCX in the mouse SVZ and SGZ [13,14]. New neurons in the SGZ were confirmed by BrdU cell tracing in non-human primates [17] and by 14C dating in humans [18]
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