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Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox‐1 homeobox transcription factor
Author(s) -
Petrova Tatiana V.,
Mäkinen Taija,
Mäkelä Tomi P.,
Saarela Janna,
Virtanen Ismo,
Ferrell Robert E.,
Finegold David N.,
Kerjaschki Dontscho,
YläHerttuala Seppo,
Alitalo Kari
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf470
Subject(s) - biology , reprogramming , lymphatic endothelium , transcription factor , microbiology and biotechnology , homeobox , lymphatic system , cancer research , cell , gene , genetics , immunology
Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo . Although these phenotypes are stable in vitro and in vivo , overexpression of the homeobox transcription factor Prox‐1 in the BECs was capable of inducing LEC‐specific gene transcription in the BECs, and, surprisingly, Prox‐1 suppressed the expression of ∼40% of the BEC‐specific genes. Prox‐1 did not have global effects on the expression of LEC‐specific genes in other cell types, except that it up‐regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox‐1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.