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By Elinor Higgins Eye on Science, FeaturesOctober 30, 2014

Skipping the stem cell step

Researchers at the Washington University School of Medicine in St. Louis have discovered a way to convert human skin cells directly to the specific type of neuron that is affected by Huntington’s disease in the brain.

The technique skips over the stem cell phase that people generally associate with being able to reprogram adult cells for other uses. This discovery could lead to massive steps in the way Huntington’s disease is being studied and treated. The disease causes the breakdown of neurons in the brain over time. According to the Huntington’s Disease Society of America, it affects approximately three to seven individuals in a population of 100,000 people of European ancestry, and fewer in other populations.

Once an individual begins to show symptoms, he or she has approximately 20 years to live, and those years will be spent in varying degrees of neuron degradation and physical deterioration, as there is no known cure. Because of how horrible Huntington’s disease is, this research is a very exciting breakthrough. Researchers have discovered a way to convert a person’s skin cells into the particular type of neuron affected by Huntington’s, the medium spiny neuron.

They have accomplished this with the use of two specific molecules of microRNA and specific transcription factors. The microRNA used are miR-9 and the miR-124. Essentially, when embryonic stem cells differentiate, or decide which type of body cell they will become, the genetic information that encodes for how to become any other type of cell is packaged away and left unused. The researchers wanted to find a way to unlock that unused information and effectively change the cell’s mind about which type of cell to be. The exposure to the two specific miRNAs alters the packaging of the DNA, allowing for the expression of other genes, including the ones that encode for becoming a neuron.

The next step is to expose the cells, now neurons, to specific transcription factors so as to specify which kind of neuron the cells should become. Transcription factors are proteins that help control the transfer of genetic information from DNA to RNA. The transcription factors that the researchers used were known to be present in the area of the brain containing the medium spiny neurons. The exposure of the neurons to the transcription factors did produce the medium spiny neurons, which researchers tested in a live model or, more specifically, mice. The converted skin cells, now neurons, were injected into the brains of mice and survived there for at least six months. 

The cells behave and look just like true medium spiny neurons and can live in a live model, not just in the lab. This could lead to potential treatments for patients and opens up new ways to study the disease. The method used to convert the skin cells into neurons is exciting because it could mean that many kinds of neurons could be produced by just changing which transcription factors are used to specify the cell.

This might be the beginning of a new line of treatments, none which require cells from outside a person’s body, thus eliminating the need for immune system-repressing drugs when such treatments take place. Research like this brings hope to those struggling with Huntington’s disease and other degenerative disorders.

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