With Great Power Comes Great Responsibility: Neural Stem Cells

Stem cells have two characteristic and essential properties:

1. Self-renewal. They can divide to give rise to another stem cell.
2. Potency. They are capable of differentiating into specialized cells.

Totipotent cells are stem cells that are capable of differentiating into all cell types in the entire organism. Pluripotent cells are descendant of totipotent cells, and are capable of differentiating into any of the three germ layers: endoderm, mesoderm and ectoderm. Further down the stem cell hierarchy are the progenitor cells whose ‘fate’ is somewhat determined. Progenitor cells have limited potency and differentiate into a specific lineage.

The neural progenitor cells (NPCs) are responsible for generating all the cell types that constitute the nervous system. Neuroepithelial cells are the earliest form of NPCs and are considered to be the stem cells of the whole nervous system. Through the timeline of development, the neuroepithelial cells are transformed into elongated radial glial cells (RG), an intermediate cell type that differentiates into more specific, lineage-determined cells of the brain. Each early RG cell divides into another RG cell and an immature neuron, which migrates out to attain maturity. Once neurons are produced, the late RG cells differentiate into glial cells – astrocytes and oligodendroglia.

While most neurogenesis ends around birth, some neural stem cells are maintained in specialized niches in the adult mammalian brain. A stem cell niche is a specialized microenvironment where the stem cell resides. Various transcriptional factors in the niche are important for stem cell survival, to retain their “stemness,” and to determine the differentiation of the housed stem cells. Much of the data about stem cell niches come from rodent research. Illustrated below are the endogenous adult stem cell niches in the rodent brain:

1. The Ventral-Subventricular zone (V-SVZ) of the lateral ventricles; which are responsible for generating olfactory bulb neurons
2. The subgranular zone (SGZ); which are involved in hippocampal neurogenesis

The endogenous stem cell niche is known to change in response to neuronal injury like cerebral ischemia or multiple sclerosis (V-SVZ). There is also a modulation in neurogenesis during mood regulation like during anxiety or stress (SGZ).

The capacity of these stem cell niches to generate neurons, albeit relatively limited, is promising for the development of therapeutic strategies towards neuronal repair. You can learn more about neural stem cells, the niche and its implications in brain repair at Dr. Fiona Doetsch’s Presidential Lecture titled, ‘Stem Cells in the Brain: Glial Identity and Niches,’ today between 5:15–6:25 PM (WCC Hall D) at the Society for Neuroscience meeting in Washington, D.C.

~

References:

Silva-Vargas V. & Fiona Doetsch (2014). A New Twist for Neurotrophins: Endothelial-Derived NT-3 Mediates Adult Neural Stem Cell Quiescence, Neuron, 83 (3) 507-509. DOI: http://dx.doi.org/10.1016/j.neuron.2014.07.029

Maldonado-Soto A.R., Derek H. Oakley, Hynek Wichterle, Joel Stein, Fiona K. Doetsch & Christopher E. Henderson (2014). Stem Cells in the Nervous System, American Journal of Physical Medicine , 93 S132-S144. DOI:http://dx.doi.org/10.1097/phm.0000000000000111

Images made by Anita Ramanathan.