Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells
Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells
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DOI：
10.1016/s0002-9440(10)63851-5
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发表时间：
2003-02-01
影响因子：
6
通讯作者：
Detmar, M
中科院分区：
文献类型：
--
作者：
Hirakawa, S;Hong, YK;Detmar, M
在哺乳动物中，淋巴血管系统是由淋巴祖内皮细胞从胚胎静脉萌芽而形成的，形成一个独特的排水血管网络，在免疫反应和癌症转移中具有重要功能。然而，血管内皮与淋巴内皮的谱系特异性分子特征仍然不明确。采用免疫磁分离法直接从人体皮肤中分离淋巴内皮细胞（LECs）和血管内皮细胞（BVECs）。体外培养的LECs在体内表达淋巴标记物Prox1和LYVE-1，并形成LYVE-1阳性的血管。转录谱研究显示，BVECs中几种细胞外基质和粘附分子的表达增加，包括versican、胶原、层粘连蛋白和N-cadherin，以及生长因子受体内啡肽和血管内皮生长因子受体-1/Fh-1。人类皮肤的差异免疫染色证实了这些基因的血管特异性表达。在胚胎发育过程中，淋巴管内皮细胞内啡肽的表达逐渐下调，而血管内皮生长因子受体-1在淋巴管中缺失。我们还发现了几个在LECs中特异表达的基因。这些结果表明，一些谱系特异性基因仅在不同的发育阶段表达，它们鉴定了血管和淋巴内皮的新分子标记，对未来血管发育和功能的研究具有重要意义。
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/Fh-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.