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Stem Cell Self-Renewal Gene Identified
By Nancy Touchette
Posted: October 30, 2003

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.

. . .

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

PubMed Abstract: Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation.
http://tinyurl.com/tcl3

Reference:

The Scientist - October 23, 2003
Bmi-1 promotes neural stem cell proliferation
Neural stem cell self-renewal is distinct from proliferation of progenitor cells
http://www.biomedcentral.com/news/20031023/01

Nature (May 2003)
http://tinyurl.com/tcgg

SOURCE: Genome News Network
http://www.genomenewsnetwork.org/articles/10_03/self_renew.shtml

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