By exposing skin cells to a particular combination of cell programming molecules, scientists managed to convert them into brain cells that behave like native cells. Share on Pinterest Human skin cells (top) can be converted into medium spiny neurons (bottom) with exposure to the right combination of microRNAs and transcription factors, according to work by Andrew Yoo and colleagues.

Image credit: Yoo Lab The study is unusual because, unlike many cell conversion techniques, the cells did not return to a stem cell stage first – they converted directly into brain cells – thus avoiding the risk of producing many other types of cells. And the study is unique, because the team managed to reprogram the skin cells to become a particular type of brain cell instead of a range of brain cells. Writing in the journal Neuron, researchers from Washington University School of Medicine in St. Louis (WUSTL), MO, report how they used a particular combination of microRNAs and transcription factors to reprogram the skin cells into a particular type of brain cell known as medium spiny neurons. The medium spiny neurons they produced – which survived for at least 6 months after injection into the brains of mice – are important for controlling movement and are the main type affected in Huntington’s disease. Huntington’s disease is an inherited genetic disease that causes involuntary movements and gradual decline of mental ability. Patients with the disease – which usually starts in middle age – can live for 20 years after symptoms begin, although these gradually get worse.

Converted cells showed properties of native cells Senior author Dr. Andrew S. Yoo, assistant professor of developmental biology at WUSTL, says not only did the new cells survive in the mouse brain, but they also showed properties similar to native cells: “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. That’s a landmark point about this paper.” Because they used adult human skin cells in the study – and not mouse cells or human cells at an earlier stage of development – the team believes the work shows the potential for using patients’ own cells in regenerative medicine. This is important because therapies can use readily available cells and also avoid the problem of immune rejection. For their study, Dr. Yoo and colleagues cultured the skin cells in an environment that mimics that of brain cells. In previous work, they had already discovered that exposing skin cells to two small RNA molecules called miR-9 and miR-124 can turn them into different types of brain cell. Although they are still trying to work out exactly what happens, the team believes the two small RNA molecules open up the tightly packed DNA inside cells that holds instructions for making brain cells, allowing the genes particular to their development and function to be switched on. Having proved that exposure to these small RNA molecules converts skin cells into a mix of brain cells, the team began fine-tuning the chemical signals. They did this by adding molecules called transcription factors that they already knew were present in the part of the brain where medium spiny neurons are abundant.