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Skin cells called fibroblasts can be transformed into neurons quickly and efficiently with just a few genetic tweaks, according to new research. The surprisingly simple conversion, which doesn’t require the cells to be returned to an embryonic state, suggests that differentiated adult cells are much more flexible than previously thought.

If the research, published in the journal Nature yesterday, can be repeated in human cells, it would provide an easier method for generating replacement neurons from individual patients. Brain cells derived from a skin graft would be genetically identical to the patient and therefore remove the risk of immune rejection–such an approach might one day be used to treat Parkinson’s or other neurodegenerative diseases.

“It’s almost scary to see how flexible these cell fates are,” says Marius Wernig, a biologist at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford, who led the research. “You just need a few factors, and within four to five days you see signs of neuronal properties in these cells.”

Three years ago, scientists shook up the stem cell field by demonstrating how to revert adult cells back to the embryonic state, using just four genetic factors. Research on these cells, known as induced pluripotent stem cells (iPS cells), has since exploded across the globe. IPS cells can be differentiated into any cell type, and show huge promise for drug screening and tissue replacement therapies. Scientists are now trying to push this newfound cellular flexibility further by converting adult cells directly from one type to another.

In 2008, Doug Melton, Qiao Zhou, and colleagues at Harvard University showed it was possible to convert one type of pancreatic cell into another, a feat that might one day help people with diabetes. The new research demonstrates a more dramatic transformation–converting skin cells into neurons. This is particularly impressive because the lineage of the two types of cells diverges very early in embryonic development. (Previous research has suggested that neurons could be made from muscle and bone marrow cells, but the fate of the cells at the end of the process was murkier.)

To create the powerful molecular cocktail, scientists started with 20 genes known to play a role in neural development and found only in the brain. All of the selected genes were transcription factors, which bind to DNA and regulate expression of other genes. Using viruses to deliver each gene into skin cells growing in a dish, the team discovered that one gene in particular had the power to convert the skin cells into what looked like immature neurons. After testing other genes in combination with the active one, scientists found a combination of three genes that could efficiently and rapidly convert skin cells into neurons.

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Credit: Thomas Vierbuchen

Tagged: Biomedicine, stem cells, iPS cells, reprogramming, regenerative medicine, neurons

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