First clues as to why stem cells ignore stop signs in the cell cycle

Jun 10 2005

Everyone knows that stem cells are controversial. Many people know that stem cells can grow into virtually any cell type found in the body, from a red blood cell to a muscle cell to a brain cell. But no one really knows why stem cells continue to divide and renew themselves long after the point where other cells stop dividing.

Now scientists at Northwestern University and the University of Washington offer one of the first clues as to why stem cells ignore stop signs in the cell cycle: a special molecular mechanism has cut the brakes. The researchers found that tiny bits of genetic material called microRNAs are necessary for stem cell division to take place, suggesting that microRNAs shut off the signals that stop cell division in most other cells.

The findings were published online this week by the journal Nature. In the paper, the researchers also speculate that microRNAs may play a similar role in cancer cells, encouraging their proliferation. This speculation is supported by three other new papers published this week in Nature linking microRNAs to cancer.

According to authors Richard Carthew, Owen L. Coon Professor of Molecular Biology at Northwestern University, and Hannele Ruohola-Baker, professor of biochemistry at the University of Washington, microRNAs can regulate gene expression and give stem cells a green light to pass from the normal stop phase to the stage in which they begin replicating their DNA for later division.

In their work, Carthew and Ruohola-Baker focused on fruit flies, which have approximately 80 types of microRNAs. They genetically modified stem cells from the fruit flies' ovaries and studied how many egg chambers the mutant stem cells produced as compared to normal stem cells. The production rate in the mutant cells fell over the course of 12 days, and the researchers concluded it was because the mutant stem cells were no longer dividing.

Without the microRNAs at work, the brakes were applied to the cell division of the mutant stem cells, just like ordinary cells. The cellular brake (in this case a protein called Dacapo, a fruit fly homologue of a human tumor suppressor) kept the stem cells from proliferating.

"Determining which of the 80 microRNAs is responsible for deactivating the stop signal is the next step of our research," said Ruohola-Baker.

"The list of chores that microRNAs do within cells keeps growing in new and surprising ways," added Carthew. "This latest discovery with stem cell division makes us wonder if microRNAs also control division of other types of cells such as cancer cells."

Other authors on the Nature paper are Kenji Nakahara of Northwestern University and Karin Fischer, Steve Hatfield and Halyna Shcherbata of the University of Washington.