Identification of Vascular Lineage-Specific Genes by Transcriptional Profiling of Isolated Blood Vascular and Lymphatic Endothelial Cells
Satoshi Hirakawa,Young-Kwon Hong,Natasha L. Harvey,Vivien Schacht,Kant Matsuda,Towia A. Libermann,Michael Detmar +6 more
TLDR
It is demonstrated that some lineage-specific genes are only expressed during distinct developmental stages and new molecular markers for blood vascular and lymphatic endothelium are identified with important implications for future studies of vascular development and function.Abstract:
In mammals, the lymphatic vascular system develops by budding of lymphatic progenitor endothelial cells from embryonic veins to form a distinct network of draining vessels with important functions in the immune response and in cancer metastasis. However, the lineage-specific molecular characteristics of blood vascular versus lymphatic endothelium have remained poorly defined. We isolated lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) by immunomagnetic isolation directly from human skin. Cultured LECs but not BVECs expressed the lymphatic markers Prox1 and LYVE-1 and formed LYVE-1-positive vascular tubes after implantation in vivo. Transcriptional profiling studies revealed increased expression of several extracellular matrix and adhesion molecules in BVECs, including versican, collagens, laminin, and N-cadherin, and of the growth factor receptors endoglin and vascular endothelial growth factor receptor-1/Flt-1. Differential immunostains of human skin confirmed the blood vessel-specific expression of these genes. During embryonic development, endoglin expression was gradually down-regulated on lymphatic endothelium whereas vascular endothelial growth factor receptor-1 was absent from lymphatics. We also identified several genes with specific expression in LECs. These results demonstrate that some lineage-specific genes are only expressed during distinct developmental stages and they identify new molecular markers for blood vascular and lymphatic endothelium with important implications for future studies of vascular development and function.read more
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Molecular regulation of angiogenesis and lymphangiogenesis.
Ralf H. Adams,Kari Alitalo +1 more
TL;DR: The angiogenic growth of blood vessels and lymphatic vessels coordinates several biological processes such as cell proliferation, guided migration, differentiation and cell–cell communication.
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Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system
TL;DR: The Tie receptors and their angiopoietin (Ang) ligands have been identified as the second vascular tissue-specific receptor Tyr kinase system and provide unique insights into the functions of this vascular signalling system.
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Lymphangiogenesis in development and human disease
Kari Alitalo,Kari Alitalo,Tuomas Tammela,Tuomas Tammela,Tatiana V. Petrova,Tatiana V. Petrova +5 more
TL;DR: The lymphatic vasculature forms a vessel network that drains interstitial fluid from tissues and returns it to the blood in an important role in the pathogenesis of several diseases, including cancer, lymphoedema and various inflammatory conditions.
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VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment
Claus Cursiefen,Lu Chen,Leonardo P. Borges,David A. Jackson,Jingtai Cao,Czeslaw Radziejewski,Patricia A. D'Amore,Reza Dana,Stanley J. Wiegand,J. Wayne Streilein +9 more
TL;DR: It is concluded that VEGF-A recruitment of monocytes/macrophages plays a crucial role in inducing inflammatory neovascularization by supplying/amplifying signals essential for pathological hemangiogenesis and lymphang iogenesis.
Journal ArticleDOI
Functionally specialized junctions between endothelial cells of lymphatic vessels
Peter Baluk,Jonas Fuxe,Jonas Fuxe,Hiroya Hashizume,Hiroya Hashizume,Talia Romano,Talia Romano,Erin Lashnits,Erin Lashnits,Stefan Butz,Dietmar Vestweber,Monica Corada,Cinzia Molendini,Elisabetta Dejana,Elisabetta Dejana,Donald M. McDonald,Donald M. McDonald +16 more
TL;DR: It is suggested that fluid enters throughoutInitial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics.
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