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Stem Cell Self-Renewal Gene Identified
  
By Nancy Touchette

Brain stem cells from mice that contain the Bmi-1 gene (top) proliferate more readily than those without the gene (bottom).

One of the most perplexing questions in stem cell biology is “What makes a stem cell a stem cell?” Researchers studying adult stem cells would like to know what distinguishes a stem cell, which can replenish itself indefinitely, from a progenitor cell, which can proliferate only a limited number of times. Now, researchers are one step closer to understanding the difference.

Researchers at the University of Michigan in Ann Arbor have identified a gene that is required for the proliferation of three types of adult stem cells from mice. Stem cells from the central nervous system, the peripheral nervous system and the blood all rely on a gene called Bmi-1 to renew themselves. However, the gene is not required for the proliferation of progenitor cells from the same tissues.

“This is the first gene identified that is consistently required by stem cells to proliferate, but it's not required by at least some types of progenitor cells,” says Sean J. Morrison, who led the research. “We expected that there would be genes like this, but it was really exciting to finally find one.”

Researchers would like to identify the genes that distinguish stem cells from progenitor cells because the two are often confused. Stem cells are more difficult to isolate because there are far fewer of them in the body, but they are considered more useful because they proliferate in culture and can replace most of the cell types of a given tissue.

Previous studies by Morrison and Michigan colleague Michael F. Clarke showed that the Bmi-1 gene is needed to maintain stem cells from the blood. The new study, reported in Nature, shows that the gene is also required by nerve stem cells from the brain and gut. The new study further shows that the gene affects the process of proliferation, but has no effect on how long a cell survives.

Maarten van Lohuizen of the Netherlands Cancer Center in Amsterdam discovered the Bmi-1 gene in cancer cells in 1991 and found that it blocks two proteins that normally inhibit cell proliferation.

Van Lohuizen also finds that the gene is needed for the renewal of stem cells. His studies also suggest that the gene is active in some cells in the cerebellum that do not appear to be stem cells.

Interestingly, many cancer cells also over express the gene. Because the gene makes cells immortal, it may play a key role in cancer development. Researchers studying both cancer and stem cells are keen on figuring out which genes are regulated by Bmi-1.

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Molofsky, A.V. et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature, published online October 22, 2003.

 

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