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Reprogrammable Cell Type Depends on a Single Gene to Keep Its Identity
Date:12/1/2008

traps and attacks invading organisms and is a primary route for malignant tumor dissemination to the regional lymph nodes.

"The new finding adds to a growing body of evidence showing that some fully differentiated cell types can exhibit great plasticity and upon reprogramming revert back to their previous identity," said Guillermo Oliver, Ph.D., a member of the St. Jude Department of Genetics and Tumor Cell Biology. Differentiation is the process by which genetic activity causes an immature cell type to acquire specific characteristics of a particular mature adult cell type.

"In the last few years, some discoveries have challenged the long-standing belief that cell differentiation is an irreversible final process," said Oliver, the paper's senior author. "St. Jude researchers showed that lymphatic endothelial cells are one of the few examples of differentiated cell types that require constant expression of a specific gene to maintain their identity. This current work builds on our previous results that demonstrated the key role Prox1 plays in the formation of the lymphatic vasculature."

As an important resource for this finding, Oliver's team used a special mouse strain in which the Prox1 genes could be deleted from LECs at different times during development or after birth.

The St. Jude team found that deletion of Prox1 in LECs promoted their reprogramming into BECs as indicated by the expression of specific LEC and BEC proteins. In addition, the newly reprogrammed cells gained some specific features typical of blood vessels. For example, the cells were surrounded by pericytes -- small cells that help support endothelial cells -- and blood abnormally entered the reprogrammed mutant lymphatic vessels.

Finally, the researchers used a trick that enabled them to block the ability of isolated cultured LECs to produce the Prox1 proteins to fur
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SOURCE St. Jude Children's Research Hospital
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