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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.
Previous Article | Next Article 
Submitted April 5, 2006
Accepted April 28, 2006
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*
Uppsala University, Department of Genetics and Pathology, Uppsala, Sweden
Karolinska Institute, Department of Medical Biochemistry and Biophysics, Stockholm, Sweden
Department of Medical Cell Biology, Uppsala University, Biomedical Center, Uppsala, Sweden
Karolinska Institute, Department of Medical Biochemistry and Biophysics/ Department of Medicine
Ludwig Institute for Cancer Research, Uppsala Branch, Uppsala, Sweden
Uppsala University, Department of Medical Cell Biology, Uppsala, Sweden
* Corresponding author; email: lena.welsh{at}genpat.uu.se.
Platelet-derived growth factor (PDGF)-BB has been
assigned a critical role in vascular stability by
promoting recruitment of PDGF receptor- -
expressing perivascular cells. Here, we present data
indicating that early hematopoietic/endothelial
(hemangio) precursors express PDGFR- based on co-
expression with CD31, vascular endothelial growth factor
receptor-2 and CD41 in two models: in the mouse yolk sac
(embryonic day, E, 8.5) and in differentiating mouse
embryonic stem cells (embryoid bodies). Expression of
PDGFR- on hemangioprecursor cells in the embryoid
bodies gradually disappeared and, at day 14, expression
appeared on perivascular cells. Activation of the PDGFR- on the hemangioprecursors accelerated
differentiation of endothelial cells whereas
differentiation of the hematopoietic lineage was
suppressed. In E9.5 yolk sacs derived from recombinant
mice expressing a 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, as compared to
staged wild type litter-mates. Moreover, enhanced
vascular remodeling was evident in the Rosa26-PDGF-B
yolk sacs. We conclude that PDGFR- is expressed
on early hemangioprecursor cells, regulating
vascular/hematopoietic development.

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