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Harvard scientists find cell fate switch that decides liver, or pancreas?

Harvard stem cell scientists have a new theory for how stem cells decide whether to become liver or pancreatic cells during development. A cell's fate, the researchers found, is determined by the nearby presence of prostaglandin E2, a messenger molecule best known for its role in inflammation and pain. The discovery, published in the journal Developmental Cell, could potentially make liver and pancreas cells easier to generate both in the lab and for future cell therapies.

Wolfram Goessling, MD, PhD, and Trista North, PhD, both principal faculty members of the Harvard Stem Cell Institute (HSCI), identified a gradient of prostaglandin E2 in the region of zebrafish embryos where stem cells differentiate into the internal organs. Experiments conducted by postdoctoral fellow Sahar Nissim, MD, PhD, in the Goessling lab showed how liver-or-pancreas-fated stem cells have specific receptors on their membranes to detect the amount of prostaglandin E2 hormone present and coerce the cell into differentiating into a specific organ type.

"Cells that see more prostaglandin become liver and the cells that see less prostaglandin become pancreas," said Goessling, a Harvard Medical School Assistant Professor of Medicine at Brigham and Women's Hospital and Dana-Farber Cancer Institute. "This is the first time that prostaglandin is being reported as a factor that can lead this fate switch and essentially instruct what kind of identity a cell is going to be."

The researchers next collaborated with the laboratory of HSCI Affiliated Faculty member Richard Maas, MD, PhD, Director of the Genetics Division at Brigham and Women's Hospital, to see whether prostaglandin E2 has a similar function in mammals. Richard Sherwood, PhD, a former graduate student of HSCI Co-director Doug Melton, was successfully able to instruct mouse stem cells to become either liver or pancreas cells by exposing them to different amounts of the hormone. Other

Contact: Joseph Caputo
Harvard University

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