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

Nicole C. Johnson, Miriam E. Dillard, Peter Baluk, Donald M. McDonald, Natasha L. Harvey, Sharon L. Frase, Guillermo Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3282-3291
Number of pages10
JournalGenes and Development
Volume22
Issue number23
DOIs
StatePublished - Dec 1 2008

Keywords

  • Blood endothelial cells
  • Lymphangiogenesis
  • Lymphatic endothelial cells
  • Prox1
  • Reprogramming
  • siRNA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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