Neuropilin-1 identifies endothelial precursors in human and murine embryonic stem cells before CD34 expression.
BACKGROUND
In murine embryonic stem cells, the onset of vascular endothelial growth factor receptor 2 (VEGFR-2) expression identifies endothelial precursors. Undifferentiated human embryonic stem cells express VEGFR-2, and VEGFR-2 expression persists on differentiation. The objective of our study was to identify a single population of endothelial precursors with common identifying features from both human and murine embryonic stem cells.


RESULTS
We report that expression of the VEGF coreceptor neuropilin-1 (NRP-1) coincides with expression of Brachyury and VEGFR-2 and identifies endothelial precursors in murine and human embryonic stem cells before CD31 or CD34 expression. When sorted and differentiated, VEGFR-2(+)NRP-1(+) cells form endothelial-like colonies that express CD31 and CD34 7-fold more efficiently than NRP-1 cells. Finally, antagonism of both the VEGF and Semaphorin binding functions of NRP-1 impairs the differentiation of vascular precursors to endothelial cells.


CONCLUSIONS
The onset of NRP-1 expression identifies endothelial precursors in murine and human stem cells. The findings define the origin of a single population of endothelial precursors from human and murine stem cells to endothelial cells. Additionally, the function of both the VEGF and Semaphorin binding activities of NRP-1 has important roles in the differentiation of stem cells to endothelial cells, providing novel insights into the role of NRP-1 in a model of vasculogenesis.
National Human Genome Research Institute, and National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Thomas
T
Cimato
Jeanette
J
Beers
Shunli
S
Ding
Mingchao
M
Ma
J Phillip
JP
McCoy
Manfred
M
Boehm
Elizabeth G
EG
Nabel
D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D039942:Neuropilin-1 / Q000235:genetics* / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D000098908:Brachyury Protein
D018952:Antigens, CD34; D015415:Biomarkers; D016895:Culture Media, Serum-Free; D005326:Fetal Proteins; D039942:Neuropilin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D039961:Semaphorins; D020825:T-Box Domain Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; D000098908:Brachyury Protein