Platelet-derived growth factor receptor-β promotes early endothelial cell differentiation

C Rolny, I Nilsson, P Magnusson, A Armulik… - Blood, 2006 - ashpublications.org
C Rolny, I Nilsson, P Magnusson, A Armulik, L Jakobsson, P Wentzel, P Lindblom, J Norlin…
Blood, 2006ashpublications.org
Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical role in vascular
stability by promoting the recruitment of PDGF receptor-β–expressing perivascular cells.
Here we present data indicating that early hematopoietic/endothelial (hemangio) precursors
express PDGFR-β based on coexpression with CD31, vascular endothelial growth factor
receptor-2, and CD41 in 2 models: mouse yolk sac (embryonic day 8 [E8]) and differentiating
mouse embryonic stem cells (embryoid bodies). Expression of PDGFR-β on …
Abstract
Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical role in vascular stability by promoting the recruitment of PDGF receptor-β–expressing perivascular cells. Here we present data indicating that early hematopoietic/endothelial (hemangio) precursors express PDGFR-β based on coexpression with CD31, vascular endothelial growth factor receptor-2, and CD41 in 2 models: mouse yolk sac (embryonic day 8 [E8]) and differentiating mouse embryonic stem cells (embryoid bodies). Expression of PDGFR-β on hemangioprecursor cells in the embryoid bodies gradually disappeared, and, at E14, expression appeared on perivascular cells. Activation of the PDGFR-β on the hemangioprecursors accelerated the differentiation of endothelial cells, whereas differentiation of the hematopoietic lineage was suppressed. In E9.5 yolk sacs derived from recombinant mice expressing kinase-active PDGFR-β with an aspartic acid to asparagine (D894N) replacement in the kinase activating loop and from mice with ubiquitous expression of PDGF-BB driven by the Rosa26 locus, the number of CD41-expressing early hematopoietic cells decreased by 36% and 34%, respectively, compared with staged wild-type littermates. Moreover, enhanced vascular remodeling was evident in the Rosa26–PDGF-BB yolk sacs. We conclude that PDGFR-β is expressed on early hemangioprecursor cells, regulating vascular/hematopoietic development.
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