RT Journal Article SR Electronic T1 Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro JF Journal of Cell Science JO J. Cell Sci. FD The Company of Biologists Ltd SP 3808 OP 3816 DO 10.1242/jcs.064279 VO 123 IS 21 A1 Cooley, Lindsay S. A1 Handsley, Madeleine M. A1 Zhou, Zhigang A1 Lafleur, Marc A. A1 Pennington, Caroline J. A1 Thompson, Erik W. A1 Pöschl, Ernst A1 Edwards, Dylan R. YR 2010 UL http://jcs.biologists.org/content/123/21/3808.abstract AB Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.