Progenitor cells: the brain beyond neurons

Researchers from John Hopkins School of Medicine, led by Dwight Bergles, have discovered how progenitor cells, a type of brain cell, remain dynamic throughout life in contrast to most neurons. Hence these cells are able to repair and replace damaged brain tissue. This function is crucial to the successful transmission of nerve signals throughout the central nervous system (CNS). Previously, progenitor cells were considered to serve merely as support and insulation to neurons. However, in March this year, scientists from University of Rochester discovered how placing human progenitor cells in a mouse’s brain could improve the mouse’s learning and memory abilities. The highly dynamic function of progenitor cells mentioned above thus seems to play an important role for higher cognitive function in humans.

In the CNS, there are two main categories of cells. One type is neurons that are responsible for the transmission of signals and thus the activity of our brains. The other type is glial cells, including progenitor cells. Progenitor cells have the ability to transform into myelin, a protective layer surrounding neurons. Myelin prevents electrical activity from ‘leaving’ the neuron and thereby increases the speed at which nerve signals travel. When myelin is damaged, progenitor cells multiply in the area and are responsible for repair.

Bergles and his team were interested in the mechanisms by which the progenitor cells remain so flexible into adulthood. How do they discover damaged tissue? And how do they maintain their numbers despite the rapid cell growth needed for repair? Using genetically modified mice with fluorescent progenitor cells, the researchers were able to observe the behaviour of the cells in real time. They found that the progenitors sense each others’ presence by moving through brain tissue and extending projections, known as filopodia. If damaged myelin is discovered within the area, they immediately multiply in order to replace and repair what is damaged.

Despite rapid multiplication, the density of progenitor cells within the brain remained stable over time. Given the tight structure of the CNS, it cannot accommodate cell growth. Uncontrolled cell growth may therefore result in brain tumours. The researchers found that progenitor cells are themselves able to perform homeostatic control of their numbers. By only triggering cell growth in response to damaged myelin and by inhibiting growth by repelling other progenitors, their density remains stable over time.

Progenitor cells are much more complex in humans than in mice. Therefore, Xiaoning Han and his team, wanted to test the significance of this difference in complexity. To do so, they grafted human progenitor cells into the forebrain of neonatal mice. The human progenitors became successfully integrated with mouse progenitors during development. The research team found that information processing in the mice with human progenitor cells was significantly faster than normal. Furthermore, these mice showed improved memory and learning of orientation in a maze compared to normal mice. Han and colleagues argue that the evolution of progenitor cells has played an important role in enabling higher cognitive function of humans.

In both mice and humans, progenitor cells play a crucial role in replacing and repairing myelin to ensure that signals travel via a neuronal network as quickly and efficiently as possible. Given the great degree of complexity difference between mice and human progenitor cells, further research will hopefully reveal which particular progenitor mechanisms boost mouse memory and learning when inserted into the brain.

References:

Hughes, E.G., Kang, S.H., Fukaya, M., and Bergles, D.E. (2013). Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nature Neuroscience, doi:10.1038/nn.3390

Han, X. et al. (2013). Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice. Cell stem cell, 12, 342-353