Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells.
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.
Hirakawa
Satoshi
S
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.
Hong
Young-Kwon
YK
Harvey
Natasha
N
Schacht
Vivien
V
Matsuda
Kant
K
Libermann
Towia
T
Detmar
Michael
M
D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D018189:Immunomagnetic Separation; D007231:Infant, Newborn; D008208:Lymphatic System / Q000166:cytology / Q000502:physiology*; D008297:Male; D017978:Receptors, Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D017978:Receptors, Growth Factor