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Molecule that restricts mouse cells' potency could yield embryonic stem cells without the sacrifice of embryos

PHILADELPHIA Scientists at the University of Pennsylvania have identified a receptor that plays a key role in restricting embryonic stem cells pluripotency, their ability to develop into virtually any of an adult animals cell types. The work is the first demonstration of a mechanism by which pluripotency is lost in mammalian embryos, one that operates with nearly the precision of an on/off switch in mouse embryos.

With further study, the receptor, dubbed GCNF, could open the door to new ways of creating embryonic stem cells without the ethical concerns associated with sacrificing embryos. GCNF, short for germ cell nuclear factor, was detailed in a recent paper in the journal Developmental Cell.

"In a sense, were hoping that understanding what GCNF actually does as it shuts down genes will let us turn back the clock on cellular development," said senior author Hans R. Schler, professor of animal biology at Penns School of Veterinary Medicine. "This knowledge may permit us to convert ordinary adult cells back to embryonic stem cells for research purposes."

Schler, also the director of Penns Center for Animal Transgenesis and Germ Cell Research, said GCNF is the first factor known to repress the key gene Oct4, which is expressed in pluripotent embryonic cells. While GCNF is likely just one cog in a complex cellular machinery that dictates pluripotency among the cells of mouse embryos, Schlers team believes it is a crucial player: without GCNF, restriction of pluripotency does not occur properly and the embryo eventually dies.

"The identification of GCNF as a repressor of Oct4 expression opens up several new avenues for understanding Oct4 regulation and, therefore, the control of the pluripotent state," wrote Peter J. Donovan of Thomas Jefferson University in an analysis appearing in the November issue of Nature Genetics. "The identification of a nexus between Oct4 and GCNF provides some critical clues as to how the di
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Contact: Steve Bradt
bradt@pobox.upenn.edu
215-573-6604
University of Pennsylvania
3-Dec-2001


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