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Insight Into Neural Stem Cells Has Implications For Designing Therapies

hod 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."

The insight, says Merkle, is a key step toward understanding the molecular mechanisms of neural stem cell potentia
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