Adult neural stem cells in the mammalian central nervous system

Abstract

Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

Figure 1

Adult NSCs in the SVZ and SGZ of the mammalian brain. (A) A schematic illustration of the adult mammalian brain in mice. Adult NSCs are primarily present in two germinal regions: the subventricular zone (SVZ) of the lateral ventricle wall and the subgranular zone (SGZ) of the hippocampal dentate gyrus. (B). Adult NSCs in the SVZ. Quiescent or dormant adult SVZ NSCs (dNSC) correspond to a unique type of cell population with cell bodies in the SVZ while contacting the ventricle through apical surfaces. They also share several common features of GFAP⁺ astrocytes and CD133⁺ ependymal cells. Actively self-renewing adult SVZ NSCs (sNSC) are located in the SVZ and give rise to neuroblasts that migrate toward the olfactory bulb. (C) Adult NSCs in the SGZ. Quiescent or dormant adult SGZ NSCs correspond to radial glia-like cells, some of which might transit to actively self-renewing adult SGZ NSCs and give rise to neuroblasts (NB) and newly generated neurons (NGN).

Figure 2

The lineage model of adult NSCs in the mammalian brain. (A). In one lineage model, adult NSCs (red, green, yellow) generated from primitive NSCs (blue) are intrinsically diverse, exhibiting vastly different developmental potential depending on their regions of distribution and developmental origins. (B). In an alternative model, adult NSCs are relatively homogenous (blue) and give rise to a heterogeneous population of lineage-restricted progenitors. (C). Under normal conditions, adult NSCs differentiate into lineage-restricted progenitors and mature neurons and glia. Lineage-restricted progenitor may revert to adult NSCs, which can be further reprogrammed into a pluripotent state under epigenetically altered conditions. Pathologically, adult NSCs or lineage-restricted progenitors may undergo genetic and epigenetic changes, transforming into tumorigenic cancer stem cells.