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Prostaglandin the key to liver versus pancreatic stem cell differentiation?
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Scientists from Harvard University have discovered that prostaglandin E2 (PGE2) is the key that unlocks stem cells to differentiate into either liver or pancreas cells. Both these cell types are derived from a common endodermal stem cell progenitor and the trigger that decides which cell fate is followed has been poorly understood up until now. This study, published in the journal Developmental Cell, may help in making it easier to generate liver and pancreas cells in the lab, with benefits for transplant patients and/or future cell therapies.

The study was initiated in zebrafish embryos, where it was observed that there was a gradient of PGE2 in the area where stem cells differentiate into the internal organs. Studies were expanded to include mouse endodermal progenitor cells. It was found that both the PGE2 synthetic enzyme cox2a and one of its receptors, ep2a, are arranged in such a way that cells closest to PGE2 synthesis become liver cells, whereas more distant cells become pancreatic. It cooperates with another cell signalling pathway, the bmp2b pathway, to favour liver versus pancreatic fate. Further experiments in mouse cells showed that PGE2 could also enhance liver growth and regeneration of liver cells. At later developmental stages, PGE2 acting via another of its receptors, the ep4a receptor, to promote both liver and pancreatic outgrowth.

Dr Wolfram Goessling, senior author on the study, said that: “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….Prostaglandin might be a master regulator of cell growth in different organs.” The researchers now plan to develop knowledge in the laboratory as to how PGE2 instructs induced pluripotent stem cells—mature cells that have been reprogrammed into a stem-like state—to become liver or pancreas cells in order to benefit transplant patients and/or future cell therapies.

Sources

NISSIM, S. et al., 2014. Prostaglandin E2 Regulates Liver versus Pancreas Cell-Fate Decisions and Endodermal Outgrowth. Developmental Cell - 13 February 2014; 10.1016/j.devcel.2014.01.006

http://www.hsci.harvard.edu/newsroom/har...r-pancreas [Accessed 17 February 2014].
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Prostaglandin the key to liver versus pancreatic stem cell differentiation?00