Scientists convert human skin cells directly into brain cells

Date: Oct-24-2014 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.

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.

Transcription factors guide the cells to become a specific type

Co-first author Matheus B. Victor, a graduate student in neuroscience,

says they believe the small RNA molecules are "doing the heavy lifting,"

and:

"They are priming the skin cells to become neurons. The transcription

factors we add then guide the skin cells to become a specific subtype, in

this case medium spiny neurons. We think we could produce different types of

neurons by switching out different transcription factors."

The team also showed that when the skin cells are exposed to the

transcription factors alone, without the small RNA molecules, the skin cells

do not convert successfully.

The team also carried out extensive tests to show the new brain cells had

the hallmarks of native medium spiny neurons. They expressed the right genes

for their specific type and did not express genes for other types of

neurons.

And, when transplanted into the brains of mice, the converted cells

looked like native medium spiny neurons and behaved like them.

The team is now using skin cells from patients with Huntington's disease

and converting them into medium spiny neurons using their new approach. They

also plan to inject the cells into mice with the disease.

The study was funded by various bodies, including the National Institutes

of Health (NIH).

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.