"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 pericytessmall cells that help support endothelial cellsand 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 further demonstrate that Prox1 activity is required by LECs to maintain their identity.
"The new insights offered by this research will give us a better understanding of how to convert one cell into another and the eventual use of the new therapeutic approaches in pathological conditions and tumors," Oliver said.
|Contact: Summer Freeman|
St. Jude Children's Research Hospital