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Stanford researchers directly turn mouse skin cells into neurons

2010-01-28 08:56 BJT

WASHINGTON, Jan. 27 (Xinhua) -- Researchers at the Stanford University School of Medicine have directly transformed mouse skin cells into functional nerve cells in a laboratory dish with the application of just three genes, according to a report published online Wednesday in journal Nature.

The cells make the change without first becoming a pluripotent type of stem cell -- a step long thought to be required for cells to acquire new identities. The finding could revolutionize the future of human stem cell therapy and recast our understanding of how cells choose and maintain their specialties in the body.

"We actively and directly induced one cell type to become a completely different cell type," said Marius Wernig, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "These are fully functional neurons. They can do all the principal things that neurons in the brain do." That includes making connections with and signaling to other nerve cells -- critical functions if the cells are eventually to be used as therapy for Parkinson's disease or other disorders.

Although previous research has suggested that it's possible to coax specialized cells to exhibit some properties of other cell types, this is the first time that skin cells have been converted into fully functional neurons in a laboratory dish. The change happened within a week and with an efficiency of up to nearly 20 percent. The researchers are now working to duplicate the feat with human cells.

"This study is a huge leap forward," said Irving Weissman, director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "The direct reprogramming of these adult skin cells into brain cells that can show complex, appropriate behaviors like generating electrical currents and forming synapses establishes a new method to study normal and disordered brain cell function. Finally we may be able to capture and study conditions like Parkinson's or Alzheimer's or heritable mental diseases in the laboratory dish for the first time."

Until recently, it's been thought that cellular specialization, or differentiation, was a one-way path: pluripotent embryonic stem cells give rise to all the cell types in the body, but as the daughter cells become more specialized, they also become more biologically isolated. Like a tree trunk splitting first into branches and then into individual leaves, the cells were believed to be consigned to one developmental fate by physical modifications -- called epigenetic changes -- added to their DNA along the way. A skin cell could no more become a nerve cell than a single leaf could flit from branch to branch or Superman could become Clark Kent in midair.

That view began to change when Dolly the sheep was cloned from an adult cell in 1997, showing that, under certain conditions, a specialized cell could shed these restrictions and act like an embryonic stem cell.

And in 2007, researchers announced the creation of induced pluripotent stem cells, or iPS cells, from human skin cells by infecting them with four stem-cell-associated proteins called transcription factors. Once the cells had achieved a pluripotent state, the researchers coaxed them to develop into a new cell type. The process was often described in concept as moving the skin cells backward along the differentiation pathway (in the leaves analogy, reversing down the branch to the tree's trunk) and then guiding them forward again along a different branch into a new lineage.