SickKids scientists uncover the key to controlling how stem cells develop



    TORONTO, Aug. 6 /CNW/ - Canadian researchers are one step closer to
controlling human embryonic stem cell differentiation thanks to the work of
scientists Dr. Cheryle Séguin and Dr. Janet Rossant of the Developmental and
Stem Cell Biology program at The Hospital for Sick Children (SickKids).
    Séguin and Rossant, along with their colleagues Dr. Jonathan Draper of
the Stem Cell and Cancer Research Institute at McMaster University, and
Dr. Andras Nagy, of Mount Sinai Hospital published these groundbreaking
findings in the Cell Press journal, Stem Cell.
    Stem cells play a critical role in human development. They are the
"master" or "parent" cells from which other cell types are derived. Human
embryonic stem cells are seen to be particularly valuable as they are
pluripotent, which means that in addition to the having the ability to
self-renew, they are also capable of developing into many different kinds of
cells in the body. These stem cells provide the starting material for every
organ and tissue, and have the potential to develop into each of the more than
200 cell types in the human body - bone, muscle, skin, blood, etc., but are
not able to form a complete organism.
    One of the biggest hurdles to overcome before the clinical use of
embryonic stem cells is our current inability to effectively control the
process of stem cell differentiation. While there has been a great deal of
research into how to coax human embryonic stem cells into becoming various
kinds of cells, this study provides a clear picture of how we might control
the early steps of endoderm tissue differentiation.
    "Our approach was to basically exploit the cell's own internal control
mechanisms to guide differentiation of the cell population as a whole," says
Dr. Séguin, a postdoctoral research fellow at SickKids and the lead author of
the study. "By manipulating the expression of transcription factors - how
genetic information is communicated within the cell - we were able to
understand how to influence to the very essence of the cell fate
determination."
    The research team focused on producing early endoderm cells from human
embryonic stem cells. Since the endoderm lineage goes on to produce essential
organs in the embryo such as the respiratory and digestive tracts, the lung,
liver and pancreas, research was directed towards generating stable progenitor
cells capable of producing all endoderm cell types. These cells were able to
maintain their distinct profiles through many stages of cell culture without
losing their ability to self renew.
    "We believe that this process provides new tools to explore the pathways
of endoderm differentiation," comments Dr. Rossant, Chief of Research at
SickKids. "We tried to make the most "immature" cell types of two different
lineages of cells in the early embryo. This way we establish a stable starting
population of cells and try to guide them through the next steps that are
required to differentiate into the mature cell types that make up various
organs."
    While this new understanding will not yet lead to use of embryonic stem
cells in human patients, this is an important step in the process. Having a
better understanding of how we manipulate cells to control how they
differentiate is an important leap and in the future will lead us into new
pathways in regenerative medicine. By studying stem cells that carry DNA with
disease-causing mutations, researchers may soon learn more about how these
mutations cause the cell to become diseased. This will also lead to research
into generating new drugs or therapies that are able to directly address the
genetic defect and treat the disease.
    This research was supported by the Canadian Institutes of Health
Research, the Stem Cell Network, the Natural Sciences and Engineering Research
Council of Canada, the Juvenile Diabetes Research Foundation, the
Biotechnology and Biological Sciences Research Council UK, and SickKids
Foundation.

    The Hospital for Sick Children (SickKids), affiliated with the University
of Toronto, is Canada's most research-intensive hospital and the largest
centre dedicated to improving children's health in the country. As innovators
in child health, SickKids improves the health of children by integrating care,
research and teaching. Our mission is to provide the best in complex and
specialized care by creating scientific and clinical advancements, sharing our
knowledge and expertise and championing the development of an accessible,
comprehensive and sustainable child health system. For more information,
please visit www.sickkids.ca. SickKids is committed to healthier children for
a better world.





For further information:

For further information: Janice Nicholson, The Hospital for Sick
Children, (416) 813-6684, janice.nicholson@sickkids.ca

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