Scientists Identify Stem Cell On/Off Switch

One gene may tell skin stem cells to change, or stay as they are

WEDNESDAY, Feb. 23, 2005 (HealthDayNews) -- The therapeutic promise of stem cells lies in the fact that they begin as undifferentiated cells, but can develop into any cell type in the body. Someday, doctors may be able to harness this process to grow replacement cells for patients who've lost tissues because of injury or disease.

However, once a stem cell differentiates into a brain, heart, muscle or other body cell, there's no turning back.

Now, in experiments with mice, scientists believe they've discovered a new class of gene signals that either prevent or permit stem cells to develop into specific cell types, according to a report in the Feb. 24 issue of Nature.

"This discovery could lead to new stem cell therapies," said lead author Deborah Lang, an instructor of medicine at the University of Chicago. Right now, she said, "we have very little understanding of how stem cells work. This is a small piece of the puzzle of how stem cells maintain their stem 'cell-ness.'"

That's important, Lang added, because to keep stem cells useful therapeutically, doctors will have to preserve them as undifferentiated stem cells for as long as possible.

In their experiments, Lang's group found that a gene called Pax3 helps maintain a reservoir of stem cells. Pax3 is present in mature skin stem cells and appears to prevent these cells from becoming full-fledged skin cells, preserving them as stem cells instead, the researchers report.

Pax3 is a gene critical in the development of melanocytes, cells that make and store the pigments in the skin and hair. It is also expressed in adult stem cells in the skin, according to the researchers.

In their experiments, Lang's team found that Pax3 directs stem cells to become melanocytes, but also prevents them from differentiating completely.

According to Lang, this is a way for the body to prevent the depletion of stem cells. "Pax3 is keeping the cells in stem-cell-like stage, so that you can still provide cells to the population but also keep some stem cells to produce more melanocytes, as needed," Lang explained.

The majority of cells in the body will eventually lose their ability to divide, she noted. But some cells don't. Like stem cells, these cells continue to grow, but they are uncontrolled. Since Pax3 is known to be involved in some cancerous tumors, this seems to imply that some cancers may begin in stem cells.

If this is correct, stem cells in the skin could be the cells that turn into skin malignancies like melanoma, Lang said, so understanding how stem cells work may also help in developing new cancer therapies.

In addition, adult stem cells are found in many types of organs and may be a potential reservoir for tissue regeneration, the Chicago researcher noted.

For example, Lang said, in the future it may be possible to use a patient's own stem cells to create replacement organs, such as a liver. This would only be possible if stem cells could be stopped from differentiating until they were needed for a specific purpose, she said.

"My idea is that this is a new family of genes -- they can both determine the cell type, but also put the brakes on differentiation," said lead researcher and co-author Dr. Jon Epstein, a professor of medicine at the University of Pennsylvania.

"We have named them pangenes, after the Greek god Pan and Peter Pan, who were able to orchestrate complex events while never growing old," he said in a prepared statement.

"It is fascinating that these embryonic genes are active in adult stem cells," said Paul Sanberg, a professor of neurosurgery and director of the University of South Florida's Center for Aging and Brain Repair. "The big issue is, can adult stem cells ever be as multipotential as embryonic stem cells? And we still don't know the answer," he added.

Sandberg believes this discovery could have far-reaching implications, however. "This same mechanism could be seen in a lot of organs," he said.

"If we can understand the Pax3 gene more, we might be able to grow cells better, because we would understand how to leave them in the state of stem cells and differentiate them when you want," Sanberg said. This finding may also aid in developing drugs that turn stem cells on, he added.

"This is far away from clinical application," Sanberg said. "But it offers new insight into drug discoveries for turning on stem cells in our own bodies and growing stem cells in the laboratory."

More information

The National Institutes of Health can tell you more about stem cells.

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