Molecule Could Yield Embryonic Stem Cells

Scientists at Penn 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 animal's 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, we're 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. Schöler, professor of animal biology at the School of Veterinary Medicine. "This knowledge may permit us to convert ordinary adult cells back to embryonic stem cells for research purposes."

Dr. Schöler, also the director of Penn's 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, Dr. Schöler's team believes it is a crucial player: without GCNF, restriction of pluripotency does not occur properly and the embryo eventually dies.

Active in a very limited population of cells, Oct4 is the only gene known to play an essential role in maintaining pluripotency. Whenever its expression is suppressed, as by GCNF, pluripotency is lost. Oct4's tightly regulated activity decreases steadily as embryonic stem cells differentiate; GCNF eventually restricts Oct4's expression in the body's somatic cells, leaving expression only in the germ cell lineage.

With President Bush's August declaration that federally funded research would be limited to stem cell lines already harvested from frozen embryos, many researchers are looking to alternative sources. Embryonic stem cells' scientific appeal lies in their pluripotency: they have not yet determined their ultimate role, so each has the potential to become one of more than 200 tissue types in the body.

Dr. Schöler was joined in the September Developmental Cell paper by Guy Fuhrmann and Ian Sylvester of Penn; Arthur C.-K. Chung, Kathy J. Jackson, Geoffrey Hummelke and Austen J. Cooney of Baylor College of Medicine; Aria Baniahmad of the University of Giessen in Germany; and Julien Sutter of the Centre du Neurochimie in Strasbourg, France. Their work was funded by the NIH, the Marion Dilley and David George Jones Funds and the Commonwealth and General Assembly of Pennsylvania.

Astronomers Unveil Dark Matter Object in the Milky Way

Astronomers from Penn, in collaboration with an international team of researchers, have made the first direct detection and measurement of the properties of a dark matter object in the Milky Way.

This observation of a gravitational microlensing event--a temporary increase in the brightness of a background star during the time it takes dark matter to pass in front of it --is reported in the Dec. 6 issue of Nature.

"By measuring its mass, distance and velocity, we have established the first complete picture of a massive compact halo object, or MACHO," said co-author Dr. Charles R. Alcock, professor of physics and astronomy at Penn. "This demonstrates that microlensing light data, high-resolution images and spectroscopy should allow astronomers to characterize a significant fraction of the Milky Way's dark matter."

Dr. Alcock, who serves as lead researcher on the international MACHO Project, made much of his contribution to the work in his previous capacity as director of the Institute of Geophysics and Planetary Physics at the Lawrence Livermore National Laboratory in California.

The team used the Hubble Space Telescope and the European Southern Observatory's Very Large Telescope to take images and make spectra of a MACHO microlens, making it possible to determine the mass of the MACHO and its distance from the Earth. In this case, the MACHO is a star 600 light-years away with a mass 5 to 10 percent the mass of the sun, making it a dwarf star and a faint member of the disk population of stars in the Milky Way.

Previous research has shown that if some of the dark matter were in the form of MACHOs, its presence could be detected by the gravitational influence MACHOs would have on light from distant stars. If a MACHO passes in front of a star in a nearby galaxy, such as the Large Magellanic Cloud, then the gravitational field of the MACHO will bend the light and focus it into telescopes.

The MACHO acts like a gravitational lens and causes the brightness of the background star to increase for the short time it takes for the MACHO to pass by. Depending on the mass of the MACHO and its distance from the Earth, this period of brightening can last days, weeks or months. Gravitational lensing can also be observed on much larger scales around large mass concentrations, such as clusters of galaxies. Since MACHOs are much smaller, they are referred to as "microlenses."

The form and duration of the brightening caused by the MACHO can be predicted by theory and searched for as a clear signal of the presence of MACHO dark matter. But in a normal event, the brightening alone is not enough information to yield the distance to the MACHO, its mass and velocity as independent quantities. It is only for unusual events, such as this one, that more can be learned.

Sachs Foundation Promotes Entrepreneurship

The Graduate School of Education and The Goldman Sachs Foundation are preparing Penn students and K-12 educators to start new initiatives in education. The Goldman Sachs Entrepreneurship in Education program will nurture entrepreneurial-minded educators and support their development of new initiatives.

"We want to give educators access to training to become successful entrepreneurs," said Nancy Streim, GSE associate dean. "Educators need to be at the forefront of reform efforts, thinking creatively about settings, products and systems for educating America's children. Then they need to get out there and do it."

A central feature is the new "education track" of the Business Plan Competition of the Wharton School. It provides mentoring, feedback and cash incentives to Penn students with ideas for new businesses in K-12 education. More than 20 teams of Penn students have drafted education-related business plans, making them eligible to win as much as $10,000 donated by The Goldman Sachs Foundation.

Other components of the Goldman Sachs Entrepreneurship in Education program include new courses that prepare Penn graduate students to start their own education-related businesses and a summer institute in entrepreneurship for K-12 teachers. In addition, a new executive-format, doctoral-degree program in educational and organizational leadership will offer and entrepreneurship concentration.

"The Goldman Sachs Foundation's partnership with Penn illustrates our commitment to excellence and innovation in education," said Stephanie Bell-Rose, president of The Goldman Sachs Foundation. "We look forward to a promising collaboration that will help shape a new generation of social entrepreneurs."

Key Risk Factor for Canine Arthritis Identified

Drawing upon an international database of some 16,000 dogs, researchers at Penn have pinpointed what's believed to be the first solid predictor, in any species, of future arthritis. The scientists have found that laxity in the hip joint--several millimeters' worth of excessive play between the ball of the femur and the hip's socket--correlates strongly with the advent of hip arthritis later in a dog's life.

"The relationship between hip laxity and arthritis in dogs is akin to the relationship between high cholesterol and heart disease in humans," said lead author Dr. Gail K. Smith, professor of orthopedic surgery and chair of the Philadelphia Department of Clinical Studies at the School of Veterinary Medicine. "Hip laxity is no guarantee of arthritis later in life, but it is a very solid risk factor."

The finding, reported in the Dec. 15 issue of the Journal of the American Veterinary Medical Association, could lead to new ways of averting or minimizing the occurrence of canine arthritis, which afflicts an estimated 70 to 80 percent of dogs in certain breeds. Since a canine generation is just 30 to 36 months, Dr. Smith said selective breeding to avoid high-laxity individuals could slash the incidence of canine arthritis within 10 years.

Dr. Smith, who began collecting data on arthritis in dogs in 1983, says the physiological similarities between dogs and humans make it very likely that joint laxity could similarly signal the likelihood of arthritis in people, whose laxity could be remedied in humans with medications. There is currently no such risk factor used to predict the onset of arthritis among humans.

"Degenerative joint disease is phenomenally prevalent in dogs," Dr. Smith said. "This work will allow breeders and pet owners to make informed decisions to help control and possibly eradicate the disease."

The current study grew out of Dr. Smith's development of a now-licensed system called the Penn Hip Improvement Program, or PennHIP. Some 1,400 veterinarians worldwide have been trained to use PennHIP to measure hip laxity among dogs; it's from these clinicians that Dr. Smith gathered data on the 15,742 dogs included in the JAVMA paper.

Penn remains the central repository for images collected using PennHIP, allowing for population studies far beyond the fewer than 100 animals involved in most veterinary studies. The number of dogs profiled in the database is growing by roughly 3,000 a year.

Dr. Smith's co-authors on the JAVMA paper include Philipp D. Mayhew, Amy S. Kapatkin, Frances S. Shofer and Thomas P. Gregor, all of the Philadelphia Department of Clinical Studies at the School of Veterinary Medicine.

MOLECULE COULD YEILD EMBRYNIC STEM CELLS | DARK MATTER OBJECT IN MILKY WAY | SACHS FOUNDATION: ENTREPRENEURSHIP | CANINE ARTHRITIS

Almanac, Vol. 48, No. 16, December 18, 2001

ISSUE HIGHLIGHTS:

Tuesday,
December 18, 2001
Volume 48 Number 16
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