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Publication : Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity.

First Author  Johnson NC Year  2008
Journal  Genes Dev Volume  22
Issue  23 Pages  3282-91
PubMed ID  19056883 Mgi Jnum  J:142041
Mgi Id  MGI:3820329 Doi  10.1101/gad.1727208
Citation  Johnson NC, et al. (2008) Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes Dev 22(23):3282-91
abstractText  The activity of the homeobox gene Prox1 is necessary and sufficient for venous blood endothelial cells (BECs) to acquire a lymphatic endothelial cell (LEC) fate. We determined that the differentiated LEC phenotype is a plastic, reprogrammable condition that depends on constant Prox1 activity for its maintenance. We show that conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages is sufficient to reprogram LECs into BECs. Consequently, the identity of the mutant lymphatic vessels is also partially reprogrammed as they acquire some features typical of the blood vasculature. siRNA-mediated down-regulation of Prox1 in LECs in culture demonstrates that reprogramming of LECs into BECs is a Prox1-dependent, cell-autonomous process. We propose that Prox1 acts as a binary switch that suppresses BEC identity and promotes and maintains LEC identity; switching off Prox1 activity is sufficient to initiate a reprogramming cascade leading to the dedifferentiation of LECs into BECs. Therefore, LECs are one of the few differentiated cell types that require constant expression of a certain gene to maintain their phenotypic identity.
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