Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation.
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.
Rolny
Charlotte
C
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv. 20, 751 85 Uppsala, Sweden. lena.welsh@genpat.uu.se.
Nilsson
Ingrid
I
Magnusson
Peetra
P
Armulik
Annika
A
Jakobsson
Lars
L
Wentzel
Parri
P
Lindblom
Per
P
Norlin
Jenny
J
Betsholtz
Christer
C
Heuchel
Rainer
R
Welsh
Michael
M
Claesson-Welsh
Lena
L
D019943:Amino Acid Substitution; D000818:Animals; D000077214:Becaplermin; D002454:Cell Differentiation; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006410:Hematopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018919:Neovascularization, Physiologic; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
D040201:Platelet Membrane Glycoprotein IIb; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2