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.