Neural stem cell

Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution.

Stem cells are characterized by their capacity to differentiate into multiple cell types. They undergo symmetric or asymmetric cell division into two daughter cells. In symmetric cell division, both daughter cells are also stem cells. In asymmetric division, a stem cell produces one stem cell and one specialized cell. NSCs primarily differentiate into neurons, astrocytes, and oligodendrocytes.

In the adult mammalian brain, the subgranular zone in the hippocampal dentate gyrus, the subventricular zone around the lateral ventricles, and the hypothalamus (precisely in the dorsal α1, α2 region and the hypothalamic proliferative region, located in the adjacent median eminence) have been reported to contain neural stem cells.

There are two basic types of stem cell: adult stem cells, which are limited in their ability to differentiate, and embryonic stem cells (ESCs), which are pluripotent and have the capability of differentiating into any cell type.

Neural stem cells are more specialized than ESCs because they only generate radial glial cells that give rise to the neurons and to glia of the central nervous system (CNS). During the embryonic development of vertebrates, NSCs transition into radial glial cells (RGCs) also known as radial glial progenitor cells, (RGPs) and reside in a transient zone called the ventricular zone (VZ). Neurons are generated in large numbers by (RGPs) during a specific period of embryonic development through the process of neurogenesis, and continue to be generated in adult life in restricted regions of the adult brain. Adult NSCs differentiate into new neurons within the adult subventricular zone (SVZ), a remnant of the embryonic germinal neuroepithelium, as well as the dentate gyrus of the hippocampus.

Adult NSCs were first isolated from mouse striatum in the early 1990s. They are capable of forming multipotent neurospheres when cultured in vitro. Neurospheres can produce self-renewing and proliferating specialized cells. These neurospheres can differentiate to form the specified neurons, glial cells, and oligodendrocytes. In previous studies, cultured neurospheres have been transplanted into the brains of immunodeficient neonatal mice and have shown engraftment, proliferation, and neural differentiation.

NSCs are stimulated to begin differentiation via exogenous cues from the microenvironment, or stem cell niche. Some neural cells are migrated from the SVZ along the rostral migratory stream which contains a marrow-like structure with ependymal cells and astrocytes when stimulated. The ependymal cells and astrocytes form glial tubes used by migrating neuroblasts. The astrocytes in the tubes provide support for the migrating cells as well as insulation from electrical and chemical signals released from surrounding cells. The astrocytes are the primary precursors for rapid cell amplification. The neuroblasts form tight chains and migrate towards the specified site of cell damage to repair or replace neural cells. One example is a neuroblast migrating towards the olfactory bulb to differentiate into periglomercular or granule neurons which have a radial migration pattern rather than a tangential one.

Neural stem cell proliferation declines as a consequence of aging. Various approaches have been taken to counteract this age-related decline. Because FOX proteins regulate neural stem cell homeostasis, FOX proteins have been used to protect neural stem cells by inhibiting Wnt signaling.