Scientists have discovered that adult neural stem cells, which exist in the brain throughout life, are not a single, homogeneous group.
Instead, they are a diverse group of cells, each capable of giving rise to specific types of neurons. The finding, the team says, significantly shifts the perspective on how these cells could be used to develop cell-based brain therapies.
The results of their study are reported online in 'science Express' and will be published in an upcoming issue of 'science."
Adult neural stem cells give rise to the three major types of brain cells' astrocytes, oligodendrocytes and neurons. Their role in producing neurons is of particular interest to scientists because neurons orchestrate brain functions -- thought, feeling and movement. If scientists could figure out how to create specific types of new neurons, they potentially could use them to replace damaged cells, such as the dopamine-producing neurons destroyed in Parkinson's disease.
In recent years, scientists have determined that adult neural stem cells are located primarily in two regions of the brain -- the lining of the brain's fluid-filled cavity, known as the subventricular zone, and a horseshoe shaped area known as the hippocampus. The laboratory of the senior author of the current study, UCSF's Arturo Alvarez-Buylla identified the stem cells in the subventricular zone in 1999 (Cell, June 11, 1999).
While scientists have known that neural stem cells in the developing brain produce particular types of neurons based on where the stem cells are located in the embryo, studies carried out in cell culture have suggested that adult neural stem cells of the fully formed brain can give rise to many types of brain cells.
In the current study, conducted in mice, the team set out to explore whether neural stem cells in different locations of the subventricular zone are all the same. They did so using a method they developed to follow the fate of early neonatal and adult neural stem cells in 15 different regions of the subventricular zone. These cells typically produce young neurons that migrate to the olfactory bulb, where they mature into several distinct types of interneurons, neurons that are essential for the sense of smell.
To the team's surprise, the adult neural stem cells in the various regions of the subventricular zone each gave rise to only very specific subsets of interneurons. Moreover, the stem cells were not susceptible to being re-specified. When they were taken out of their niche and transplanted into another region of the subventricular zone, they continued to produce the same subset of interneurons. Similarly, they retained their specialized production of distinct subtypes of neurons when removed from the animals' brains and exposed to a cocktail of growth factors in a culture dish.
The findings, says the lead author of the study, Florian T. Merkle a graduate student in the Alvarez-Buylla lab, suggests that while adult neural stem cells of the subventricular zone can produce the three major types of brain cells -- astrocytes, neurons and oligodendrocytes' when it comes to neurons they seem to be specified, or programmed, to produce very specific subtypes.
"The data supporting the finding is remarkably clean and was highly unexpected," says senior author Alvarez-Buylla, UCSF Heather and Melanie Muss Professor of Neurological Surgery."We've been studying this region of the brain for many years and Florian's data has produced a different scenario, so we have to readjust now."
"We should abandon the idea that these cells are good for making any kind of neuron. This is just not going to be the case unless we find ways to reprogram these cells genetically."