Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation
2006 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 108, no 6, 1877-1886 p.Article in journal (Refereed) Published
Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical role in vascular stability by promoting the recruitment of PDGF receptor-beta-expressing perivascular cells. Here we present data indicating that early hematopoietic/endothelial (hemangio) precursors express PDGFR-beta 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-beta on hemangioprecursor cells in the embryoid bodies gradually disappeared, and, at E14, expression appeared on perivascular cells. Activation of the PDGFR-beta 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-beta 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-beta is expressed on early hemangioprecursor cells, regulating vascular/hematopoietic development.
Place, publisher, year, edition, pages
2006. Vol. 108, no 6, 1877-1886 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-19763DOI: 10.1182/blood-2006-04-014894ISI: 000240394800023PubMedID: 16690964OAI: oai:DiVA.org:uu-19763DiVA: diva2:47535