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(Circulation. 2009;119:2170-2178.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

Neuropilin-1 Identifies Endothelial Precursors in Human and Murine Embryonic Stem Cells Before CD34 Expression

Thomas Cimato, MD, PhD; Jeanette Beers, PhD; Shunli Ding, PhD; Mingchao Ma, MD, PhD; J. Phillip McCoy, PhD; Manfred Boehm, MD; Elizabeth G. Nabel, MD

From the National Human Genome Research Institute (T.C., J.B., E.G.N.) and National Heart, Lung, and Blood Institute (T.C., S.D., M.M., J.P.M., M.B., E.G.N.), Bethesda, Md.

Correspondence to Elizabeth G. Nabel, MD, Vascular Biology and Genomics Section, National Human Genome Research Institute, and National Heart, Lung, and Blood Institute, National Institutes of Health, 31 Center Dr, Building 31/Room 5A48, Bethesda, MD 20892. E-mail nhlbiiod{at}mail.nih.gov

Received September 19, 2007; accepted January 16, 2009.

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.

Methods and 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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2009 119: 2125-2126. [Extract] [Full Text]

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