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Newly-discovered class of genes determines and restricts stem cell fate

(Philadelphia, PA) Research on adult stem cells found in the skin hints at a new class of genes, according to a study from investigators at the University of Pennsylvania School of Medicine. These genes dubbed pangenes can both govern a stem cell's fate and put a hold on future differentiation until the time is right. Understanding the molecular control of these genes has implications for therapies that involve tissue regeneration.

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

"Our findings told us that a recapitulation of an embryonic program is occurring in resident stem cells in adult skin," explains Jon Epstein, MD, Professor of Medicine, Cardiovascular Division. "These few rare stem cells were expressing genes that previously had only been known to be expressed in a developing embryo. That was the first clue that we were on to something new." Epstein and colleagues report their findings in the February 24th issue of Nature.

The scientists found that Pax3 plays dual and somewhat seemingly contradictory roles in adult stem cells: it directs them to become melanocytes, but simultaneously prevents them from differentiating completely. "It gets the show going, but at the same time, prevents the final act," says Epstein. "I call this dual function a "biological capacitor," because Pax3 tells the cell: Get ready to go, but at the same time won't let it proceed."

Pangenes Express Behavioral Qualities of Pan and Peter Pan

Epstein notes that this research is conceptually new since he suggests that a single gene can both tell a cell what it should become and restrict its fate by preventing differentiation. The ability of a single biochemical factor or complex of factors to have this dual role may represent a new general paradigm for developmental and stem
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Contact: Ed Federico
ed.federico@uphs.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
23-Feb-2005


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