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Pancreatic Lineage Specification from Endoderm-Committed ES Cells

Funding:

National Institutes of Health

Principal Investigator:

Jon S. Odorico

Lab Website:

(Lab website not available at this time)

Project Summary:

In Type I diabetes, b cells within islets of the pancreas are permanently damaged. Insulin-replacement therapies, including islet and pancreas transplantation, are largely successful in restoring normal glucose metabolism, but the scarcity of donor organs restricts their use. A major goal of diabetes research is to generate an unlimited supply of insulin-producing b cells or islet cells that could be used for transplantation. Embryonic stem cells (ESCs) can proliferate indefinitely in culture, yet are able to turn into many distinct mature cell types under appropriate conditions. Our research has shown that ESCs are capable of differentiating into pancreatic precursor cells and islet hormone-producing cells, and could thus potentially be used to generate an abundant supply of islet tissue. However, using current culture protocols, the percentage of cells adopting a pancreatic fate is less than 1%.

Of the cell types present in the very early embryo and ESC cultures, only endoderm cells can become pancreatic cells. Thus, to increase the percentage of b -like cells, we will isolate endoderm cells from ESC cultures. We will activate important pancreatic genes in the selected endoderm cells, and determine whether this results in a greater percentage of cells adopting a pancreatic fate, as we expect. We will also study the cells in which the pancreatic genes have been turned on, which will aid us in understanding exactly how the mammalian pancreas forms. A more complete knowledge of pancreas formation will ultimately aid us in our efforts to generate b cells from ESCs.

 

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First published: 07/15/02 Last updated: 11/24/09 webmaster@surgery.wisc.edu
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