N-cadherin deficiency impairs pericyte recruitment, and not endothelial differentiation or sprouting, in embryonic stem cell-derived angiogenesis |
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Authors: | Tillet Emmanuelle Vittet Daniel Féraud Olivier Moore Robert Kemler Rolf Huber Philippe |
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Affiliation: | Laboratoire de Développement et Vieillissement de l'Endothelium, INSERM EMI 0219; CEA; Joseph Fourier University, Grenoble, France. emmanuelle.tillet@cea.fr |
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Abstract: | Endothelial cells express two classical cadherins, VE-cadherin and N-cadherin. VE-cadherin is absolutely required for vascular morphogenesis, but N-cadherin is thought to participate in vessel stabilization by interacting with periendothelial cells during vessel formation. However, recent data suggest a more critical role for N-cadherin in endothelium that would regulate angiogenesis, in part by controlling VE-cadherin expression. In this study, we have assessed N-cadherin function in vascular development using an in vitro model derived from embryonic stem (ES) cell differentiation. We show that pluripotent ES cells genetically null for N-cadherin can differentiate normally into endothelial cells. In addition, sprouting angiogenesis was unaltered, suggesting that N-cadherin is not essential for the early events of angiogenesis. However, the lack of N-cadherin led to an impairment in pericyte covering of endothelial outgrowths. We conclude that N-cadherin is necessary neither for vasculogenesis nor proliferation and migration of endothelial cells but is required for the subsequent maturation of endothelial sprouts by interacting with pericytes. |
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Keywords: | N-cadherin Angiogenesis Embryonic stem cell Pericyte |
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