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
“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
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
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