(Philadelphia, PA) - The difference between a group of 'blank' stem cells and a developing fetus is a complex series of biochemical reactions that transform stem cells into specific types of body tissue. In this week's issue of Science, researchers at the University of Pennsylvania Medical Center report how the enzyme QSulf1 fits into this biochemical clockwork, helping cells respond to one of the many chemical signals that surround them.

"It is a problem at the heart of basic biology - how one cell becomes muscle while an adjacent cell turns to bone," said Charles P. Emerson, PhD, Joseph P. Leidy Professor of Biology and Chair of Penn's Department of Cell and Developmental Biology. "For all we know of stem cells and the molecules involved in cell differentiation, we know very little about how these processes physically work."

As an embryo develops, different molecular signals instruct cells to produce proteins that will transform the cell into a particular tissue type, such as bone or muscle. QSulf1 functions in progenitor cells, slightly more advanced forms of stem cells that have fewer potential career paths.

According to the researchers, QSulf1 represents a new class of enzymes whose main function is to modify an important signaling co-factor, called heparan sulfate proteoglycans (HSPG). It is a small yet important step in a chain of reactions involved in allowing a cell to respond to a specific molecular signal, Wnt, and transforming the cell into muscle, instead of skin or bone.

"It is not enough to know what proteins are involved in embryonic development, we must understand how they work in order to eventually understand how to fix them when they fail," said Emerson.

Based on their findings, the researchers propose that Qsulf1 is released onto the surface
of specific embryonic cells where it snips off a specific sulfur-containing chemical group (called a sulfate group) that projects from a specific part of the HSPG molecule.

As a result, Wnt signaling molecules, which are bound to HSPGs on surface of cells, are released, allowing Wnts to activate regulatory genes that give career instructions. In this study, the researchers show that QSulf1 allows embryonic cells to express a muscle master regulatory gene called MyoD, which then instructs these cells to become muscle progenitor cells instead of a skin or bone progenitor cells.

These findings are not only of interest to researchers in the fields of cell biology and developmental diseases, but also highlights how much remains to be learned about complex workings of the developing embryo.

Emerson and his colleagues first identified QSulf1 as they studied bird embryos for genes whose expression is controlled by Shh, a molecule of known importance in developmental processes. Interestingly, the QSulf1 gene remains essentially unchanged within the genomes of worms, flies, mice, and humans.

"Evolution has seen fit to keep this protein around a long time," said Emerson. "What we see is the emerging picture of a fundamental player in the embryonic development of many types of organisms."

Understanding the mechanisms of stem cell specification will unlock potential new technologies for the repair of organs and tissues damaged by disease and trauma.

"If we are going to use stem cells to treat developmental disorders, there is still a great deal that basic biology must tell us," said Emerson. "We are only now beginning to understand how the body builds tissues."

The research was funded by the National Institutes of Health and the Royal Society and Welcome Trust.

Other Penn scientists who participated in the study are Marcus K. Gustafsson; Weitao Sun; Xingbin Ai, PhD, and David M. Standiford, PhD. Gurtej K. Dhoot, PhD, of the Royal Veterinary College, University of London, also collaborated in the research.

# # #

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.

Share This Page: