Scientists find key to stem cell immortality

How microRNAs work
In a cell's molecular machinery, strands of ribonucleic acid, or RNA, help turn the genetic code contained in DNA's double helix into instructions for making the proteins needed by the cell. MicroRNAs are short bits of RNA that are thought to act as control dials for the machinery. About 200 human microRNAs have been identified, but researchers are still trying to figure out exactly what they do.

"Nine years ago, we knew nothing about microRNAs," Ruohola-Baker said. "It is a system that is totally against the conventional dogma of biology. They are made to stop other RNA from making proteins."

Ruohola-Baker's research focuses on fruit flies, which have about 80 types of microRNA. She and her colleagues from the University of Washington and Northwestern University genetically modified female fruit flies so that their ovaries produced normal stem cells as well as stem cells in which the microRNAs were deactivated. Then they compared how many egg chambers were produced by each type of stem cells.

The results showed a falling egg production rate over the course of eight to 12 days, and the researchers determined that was because the mutant stem cells were no longer dividing.

The stem cells didn't transform themselves into different types of cells, Ruohola-Baker said: "They kept their 'stem-cellness.' The only thing that was wrong is that they did not divide."

The researchers concluded that when the microRNAs were knocked out of commission, the stem cells obeyed the same stop signal that kept other types of cells from proliferating. Their experiments indicated that a protein called Dacapo — the fruit fly's equivalent of a human tumor suppressor — served as the stop signal.

But exactly which of the fruit fly's 80 microRNAs is responsible for short-circuiting the stop signal and keeping stem cells dividing? That's one of the questions Ruohola-Baker and her colleagues plan to address next. Ruohola-Baker said they'll focus first on five likely suspects that were identified through computer simulations of the cell's chemical interactions.

Help for aging stem cells?
And now that the researchers have found that too few microRNAs are bad for stem cells, they want to see what an abundance of microRNAs will do. Perhaps the right recipe can give even ordinary cells a touch of "stem-cellness."

"We are right now testing that, by overproducing microRNAs in the daughter cells that have begun to differentiate," Ruohola-Baker said. "Maybe this would also help aging stem cells. Maybe you can keep them dividing by using more microRNAs."

Ruohola-Baker's colleagues on the research team are Steve Hatfield, Halyna Shcherbata and Karin Fischer of the University of Washington; and Richard Carthew and Kenji Nakahara of Northwestern University.

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