| February 23, 2005
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-cell biology. “My idea is that this is
a new family of genes—they can both determine
the cell type, but also put the breaks on differentiation,”
says Epstein. “We have named them pangenes, after
the Greek god Pan and Peter Pan, who were able to orchestrate
complex events while never growing old.”
Epstein thinks that this concept may also be important
for understanding the cell of origin for a number of
tumors. Pax3 is known to be involved in some
tumors, 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.
Adult resident stem cells have been identified in many
types of organs and may be a potential reservoir for
tissue regeneration. A fundamental understanding of
the molecular programs that regulate stem-cell differentiation
is necessary for harnessing this potential.
This work was supported by grants from the National
Institutes of Health. Epstein’s coauthors are
Deborah Lang, Min Min Lu, Li Huang, Kurt A. Engleka,
Maozhen Zhang, Emily Y. Chu, and Sarah Millar from Penn;
and Shari Lipner and Arthur Skoultchi from the Albert
Einstein College of Medicine.
For
a printer friendly version of this release,
click
here.
###
PENN Medicine is a $2.7 billion
enterprise dedicated to the related missions of medical
education, biomedical research, and high-quality patient
care. PENN Medicine consists of the University of Pennsylvania
School of Medicine (founded in 1765 as the nation’s
first medical school) and the University of Pennsylvania
Health System (created in 1993 as the nation’s
first integrated academic health system).
Penn’s School of Medicine is ranked #3 in the
nation for receipt of NIH research funds; and ranked
#4 in the nation in U.S. News & World Report’s
most recent ranking of top research-oriented medical
schools. Supporting 1,400 fulltime faculty and 700 students,
the School of Medicine is recognized worldwide for its
superior education and training of the next generation
of physician-scientists and leaders of academic medicine.
Penn Health System is comprised of: its flagship hospital,
the Hospital of the University of Pennsylvania, consistently
rated one of the nation’s “Honor Roll”
hospitals by U.S. News & World Report; Pennsylvania
Hospital, the nation's first hospital; Presbyterian
Medical Center; a faculty practice plan; a primary-care
provider network; two multispecialty satellite facilities;
and home health care and hospice.
|
