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Master regulatory gene of epithelial stem cells identified
Findings
have implications for adult stem cell renewal and cancers
Friday, 04 May 2007
CellNEWS — The skin’s ability to
replace the tissue it sloughs off is controlled by a variety of genes. A
new study from Harvard Medical School published in the May 4 issue of Cell,
however, identifies a "master
regulator" of this regeneration process not only for skin, but for
many epithelial tissues including breast, prostate, and urogenital tract. This
master regulator of epithelial stem cells turns out to be the p63 gene, a close relative to the
well-known tumour-suppressing p53 gene. Without p63, mutant mice run out of
the regenerative epithelial stem cells. The findings also have implications
for cancers of the skin, breast and prostate, which are among the most
common human malignancies.
The role of p63 in epithelial stem cells has been controversial. Some
studies found that p63 maintains a steady pool of the regenerative cells,
while other studies argued that p63 has more to do with causing the cells
to differentiate into particular types of tissue. The study, which was lead
by Frank McKeon, PhD, professor
of cell biology at Harvard Medical School (HMS), shows that p63’s role in
not in tissue differentiation but rather to impart "stemness" to the regenerative cells in these
tissues.
"With the p63-lacking mice you
get normal commitment and differentiation," says McKeon.
"The defect is simply running
out of stem cells. When you run out of stem cells, you run out of those
tissues as we have seen with the mice lacking the p63 gene."
Having established that p63 was only important to the maintenance of stem
cells, McKeon and his research team then used the epithelial stem cell
cloning methods developed by Howard Green, MD, the George Higginson
professor of cell biology at HMS, to show that p63’s key function was to
provide the enhanced potential of stem cells to divide.
"The fact that p63 is essential
for these epithelial stem cells, while other master regulators have been
identified for blood stem cells and spermatocyte stem cells, suggests a
fundamental requirement for tissue specificity of these regulators that we
don’t understand," says McKeon.
"Dissecting the genetic programs
controlled by these regulators will tell us much about how stem cells
function and how they go awry in cancer."
This work was supported by the National Institutes of Health.
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