LymphedemaV1, Main, Exploration, bibRecord, 006A48

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

Identifieur interne : 006A48 ( Main/Exploration ); précédent : 006A47; suivant : 006A49

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

Auteurs : Nicole C. Johnson [États-Unis] ; Miriam E. Dillard [États-Unis] ; Peter Baluk [États-Unis] ; Donald M. Mcdonald [États-Unis] ; Natasha L. Harvey [Australie] ; Sharon L. Frase [États-Unis] ; Guillermo Oliver [États-Unis]

Source :

Genes & Development [ 0890-9369 ] ; 2008.

RBID : PMC:2600759

Abstract

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600759

DOI: 10.1101/gad.1727208
PubMed: 19056883
PubMed Central: 2600759

Affiliations:

Australie, États-Unis

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>The activity of the homeobox gene <italic>Prox1</italic>
 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 <italic>Prox1</italic>
 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 <italic>Prox1</italic>
-dependent, cell-autonomous process. We propose that <italic>Prox1</italic>
 acts as a binary switch that suppresses BEC identity and promotes and maintains LEC identity; switching off <italic>Prox1</italic>
 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.</p>
</div>
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Serveur d'exploration sur le lymphœdème

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

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

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Abstract

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