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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1877-1886.
Prepublished online as a Blood First Edition Paper on May 11, 2006; DOI 10.1182/blood-2006-04-014894.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Platelet-derived growth factor receptor- promotes early endothelial cell differentiation
Charlotte Rolny,
Ingrid Nilsson,
Peetra Magnusson,
Annika Armulik,
Lars Jakobsson,
Parri Wentzel,
Per Lindblom,
Jenny Norlin,
Christer Betsholtz,
Rainer Heuchel,
Michael Welsh, and
Lena Claesson-Welsh
From the Department of Genetics and Pathology and the Department of Medical Cell Biology, Uppsala University; the Department of Medical Biochemistry and Biophysics and the Department of Medicine, Karolinska Institute, Stockholm; and the Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical role in vascular stability by promoting the recruitment of PDGF receptor- expressing perivascular cells. Here we present data indicating that early hematopoietic/endothelial (hemangio) precursors express PDGFR- 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- on hemangioprecursor cells in the embryoid bodies gradually disappeared, and, at E14, expression appeared on perivascular cells. Activation of the PDGFR- 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- 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 Rosa26PDGF-BB yolk sacs. We conclude that PDGFR- is expressed on early hemangioprecursor cells, regulating vascular/hematopoietic development.

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