Genes that determine and restrict stem cell fate 7/3/05. By the University of Pennsylvania School of Medicine Research on adult stem cells found in the skin hints at a new class of genes – dubbed pangenes – that can both govern a stem cell's fate and put a hold on future differentiation until the time is right.

Researchers at the University of Pennsylvania School of Medicine found that Pax3, a gene critical in embryonic development of cells that make and store the pigments in the skin and hair (melanocytes) is also expressed in adult stem cells in the skin.

"These few rare [adult] stem cells were expressing genes that previously had only been known to be expressed in a developing embryo," said Jon Epstein, Professor of Medicine. "That was the first clue that we were on to something new."

Understanding the molecular control of these genes has implications for therapies that involve tissue regeneration. Epstein and colleagues reported 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. "Pax3 tells the cell: Get ready to go, but at the same time won't let it proceed."

Epstein thinks that this concept may also be important for understanding the cell of origin for a number of tumours. Pax3 is known to be involved in some tumours, which adds evidence to the stem-cell origin for some cancers. This theory proposes that many cancers may arise from normally scarce resident stem cells that grow uncontrollably, rather than from the vast majority of differentiated cells that make up organs where cancers are found.

If this theory is correct, resident stem cells in the skin could be the cells that turn into skin cancers like melanoma. Understanding stem cell biology may therefore be important for developing new therapies for cancer.

Adapted from a news release by the University of Pennsylvania School of Medicine .

Links

Lang D, et al. (2005) Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433: 884-7. Abstract

Jonathan Epstein research page