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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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Submitted April 5, 2006
Accepted April 28, 2006

Platelet-derived growth factor receptor-{beta} 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-{beta}- expressing perivascular cells. Here, we present data indicating that early hematopoietic/endothelial (hemangio) precursors express PDGFR-{beta} 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-{beta} on hemangioprecursor cells in the embryoid bodies gradually disappeared and, at day 14, expression appeared on perivascular cells. Activation of the PDGFR-{beta} 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-{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, 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-{beta} is expressed on early hemangioprecursor cells, regulating vascular/hematopoietic development.


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PDGFRbeta: a multifaceted player in vascular and hematopoietic development
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