Salk researchers reprogram adult stem cells in their natural e...(m one neuron to the next. They form a fa...)

When pampered and cosseted in a petri dish, adult neural stem cells can be nudged to differentiate into any kind of brain cell but within their natural environment in the brain career options of neural stem cells are thought to be mostly limited to neurons.

"When we grow stem cells in the lab, we add lots of growth factors resulting in artificial conditions, which might not tell us a lot about the in vivo situation," explains first author Sebastian Jessberger, M.D., formerly a post-doctoral researcher in Gage's lab and now an assistant professor at the Institute of Cell Biology at the Swiss Federal Institute of Technology in Zurich. "As a result we don't know much about the actual plasticity of neural stem cells within their adult brain niche."

To test whether stem cells in their adult brain environment can still veer off the beaten path and change their fate, Jessberger used retroviruses to genetically manipulate neural stem cells and their progeny in the dentate gyrus of laboratory mice. Under normal conditions, the majority of newborn cells differentiated into neurons. When he introduced the Ascl1, which had previously been shown to be involved in the generation of oligodendrocytes and inhibitory neurons, he successfully redirected the fate of newborn cells from a neuronal to an oligodendrocytic lineage.

"It was quite surprising that stem cells in the adult brain maintain their fate plasticity and that a single gene was enough to reprogram these cells," says Jessberger. "We can now potentially tailor the fate of stem cells to treat certain conditions such as multiple sclerosis."

In patients with multiple sclerosis, the immune system attacks oligodendrocytes, which leads to the thinning of the myelin layer affecting the neurons' ability to efficiently conduct electrical
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