Human Skin Cells Reprogrammed Directly Into Brain Cells

Posted: October 23, 2014 at 8:42 am

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Newswise Scientists have described a way to convert human skin cells directly into a specific type of brain cell affected by Huntingtons disease, an ultimately fatal neurodegenerative disorder. Unlike other techniques that turn one cell type into another, this new process does not pass through a stem cell phase, avoiding the production of multiple cell types, the studys authors report.

The researchers, at Washington University School of Medicine in St. Louis, demonstrated that these converted cells survived at least six months after injection into the brains of mice and behaved similarly to native cells in the brain.

Not only did these transplanted cells survive in the mouse brain, they showed functional properties similar to those of native cells, said senior author Andrew S. Yoo, PhD, assistant professor of developmental biology. These cells are known to extend projections into certain brain regions. And we found the human transplanted cells also connected to these distant targets in the mouse brain. Thats a landmark point about this paper.

The work appears Oct. 22 in the journal Neuron.

The investigators produced a specific type of brain cell called medium spiny neurons, which are important for controlling movement. They are the primary cells affected in Huntingtons disease, an inherited genetic disorder that causes involuntary muscle movements and cognitive decline usually beginning in middle-adulthood. Patients with the condition live about 20 years following the onset of symptoms, which steadily worsen over time.

The research involved adult human skin cells, rather than more commonly studied mouse cells or even human cells at an earlier stage of development. In regard to potential future therapies, the ability to convert adult human cells presents the possibility of using a patients own skin cells, which are easily accessible and wont be rejected by the immune system.

To reprogram these cells, Yoo and his colleagues put the skin cells in an environment that closely mimics the environment of brain cells. They knew from past work that exposure to two small molecules of RNA, a close chemical cousin of DNA, could turn skin cells into a mix of different types of neurons.

In a skin cell, the DNA instructions for how to be a brain cell, or any other type of cell, is neatly packed away, unused. In past research published in Nature, Yoo and his colleagues showed that exposure to two microRNAs called miR-9 and miR-124 altered the machinery that governs packaging of DNA. Though the investigators still are unraveling the details of this complex process, these microRNAs appear to be opening up the tightly packaged sections of DNA important for brain cells, allowing expression of genes governing development and function of neurons.

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Human Skin Cells Reprogrammed Directly Into Brain Cells

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