Toronto, ON – Canadian researchers are one step closer to controlling human embryonic stem cell differentiation thanks to the work of scientists Dr Cheryle Sguin and Dr Janet Rossant of the developmental and stem cell biology program at the Hospital for Sick Children (SickKids).
Drs Sguin 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.
“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 Sguin, 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.
The 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.