Gene that directs fate of many embryonic stem cells identified

Scientists have identified the gene that prompts embryonic stem cells to generate precursors to most internal organs. The finding suggests a potent new way of coaxing stem cells to produce high numbers of specialized cells that can form medically needed tissues such as insulin-producing pancreatic cells, the scientists say.

The research led by University of California, San Francisco scientists is based on studies of zebrafish, an animal that has become a powerful model of early human embryo development. Strong evidence indicates that the pivotal gene plays the same role in humans as it does in zebrafish: inducing embryonic stem cells to produce endoderm, the source material for many specialized cells and tissues, including the pancreas, liver, thymus and thyroid.

"Exploiting this master gene, we can control stem cell differentiation from the inside, as opposed to trying to boost differentiation from the outside with growth factors," said Didier Stainier, PhD, UCSF associate professor of biochemistry and biophysics and senior author on a paper reporting the research. The study is published in the June 15 issue of Genes and Development.

Embryonic stem cells are the focus of intense research interest because their ability to give rise to all tissues of the body make them a potentially vital player in regenerative medicine.

The researchers dubbed the master gene they isolated casanova because mutant animals lacking the gene have a split heart. Casanova or cas, the team found, is essential and sufficient to prod embryonic stem cells into making endodermal cells. These, in turn, give rise to many internal organs, as well as the lining of the lungs and gut.

Ambitious new efforts to restore the insulin-producing capacity in people with type 1 diabetes rely on injections of insulin-producing beta cells. But the supply of these cells is severely limited. Endoderm gives rise to these beta cells, and also to the liver's hepatocytes. By

Contact: Wallace Ravven
University of California - San Francisco

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