Anatomical perspectives on adult neural stem cells

Abstract

The concept of stem cells within the adult brain is not new. However, only recently have scientific techniques become sufficiently advanced to identify them although this remains problematic and the technology is still developing. Nevertheless, it is now generally recognized that stem cells are restricted to two germinal regions within the intact brain. From here they can migrate to specific destinations where they integrate with existing circuitry. Their identity remains controversial but a growing body of evidence suggests it may have an astrocytic phenotype. Within the germinal regions the stem cells are confined to a niche environment and are capable of responding to environmental signals generated locally in an autocrine or paracrine fashion. The niche environment is also modulated by more generalized systemic and physiological activity. These observations are exciting in their own right and form the basis of this review. They are also beginning to alter how we think about neural injury and disease and to impact on the development of novel therapies.

Fig. 1

In the adult brain, stem cell-like astrocytes divide asymmetrically to maintain a population of slowly dividing precursors in the germinal niche. A transient population of rapidly dividing cells can also be generated that can migrate away from the germinal niche and differentiate into functionally mature neurons and glia.

Fig. 2

Neural epithelial cells evolve into radial glia which give rise to astrocytes. Both radial glia and astrocytes divide asymmetrically to produce both glia and neurons. These cells may be produced directly or via a transit amplifying population. In humans and other mammalian species the radial glia are lost in the perinatal period. It is now thought that they transform into a subpopulation of astrocytes that retain the ability to produce neurons and glia.

Fig. 3

Current concept of the stem cell niche. The multipotent stem cell-like astrocytes are closely opposed to the ventricular lining and basal lamina associated with the pial microvasculature. Asymmetric division gives rise to self-renewal (green arrow) and a transit amplifying population (blue arrow). These cells can migrate out of the germinal niche and differentiate into neurons and glia (brown arrows).