Furuhata Souichi, Ando Kiyoshi, Oki Masayuki, Aoki Kazunori, Ohnishi Shunsuke, Aoyagi Kazuhiko, Sasaki Hiroki, Sakamoto Hiromi, Yoshida Teruhiko, Ohnami Shumpei
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
Mol Cell Biochem. 2007 Apr;298(1-2):125-38. doi: 10.1007/s11010-006-9359-4. Epub 2007 Jan 3.
Among the many tissue stem or progenitor cells recently being unveiled, endothelial progenitor cells (EPCs) have attracted particular attention, not only because of their cardinal role in vascular biology and embryology but also because of their potential use in the therapeutic development of a variety of postnatal diseases, including cardiovascular and peripheral vascular disorders and cancer. The aim of this study is to provide some basic and comprehensive information on gene expression of EPCs to characterize the cells in molecular terms. Here, we focus on EPCs derived from CD34-positive mononuclear cells of human umbilical cord blood. The EPCs were purified and expanded in culture and analyzed by a high-density oligonucleotide microarray and real-time RT-PCR analysis. We identified 169 up-regulated and 107 down-regulated genes in the EPCs compared with three differentiated endothelial cells of human umbilical vein endothelial cells (HUVEC), human lung microvascular endothelial cells (LMEC) and human aortic endothelial cells (AoEC). It is expected that the obtained list include key genes which are critical for EPC function and survival and thus potential targets of EPC recognition in vivo and therapeutic modulation of vasculogenesis in cancer as well as other diseases, in which de novo vasculogenesis plays a crucial role. For instance, the list includes Syk and galectin-3, which encode protein tyrosine kinase and beta-galactoside-binding protein, respectively, and are expressed higher in EPCs than the three control endothelial cells. In situ hybridization showed that the genes were expressed in isolated cells in the fetal liver at E11.5 and E14.5 of mouse development.
在最近发现的众多组织干细胞或祖细胞中,内皮祖细胞(EPCs)受到了特别关注,这不仅是因为它们在血管生物学和胚胎学中具有重要作用,还因为它们在多种产后疾病(包括心血管和外周血管疾病以及癌症)的治疗开发中具有潜在用途。本研究的目的是提供一些关于EPCs基因表达的基础且全面的信息,以便从分子层面表征这些细胞。在这里,我们聚焦于源自人脐带血CD34阳性单核细胞的EPCs。将这些EPCs进行纯化并在培养中扩增,然后通过高密度寡核苷酸微阵列和实时逆转录-聚合酶链反应分析进行检测。与三种分化的内皮细胞——人脐静脉内皮细胞(HUVEC)、人肺微血管内皮细胞(LMEC)和人主动脉内皮细胞(AoEC)相比,我们在EPCs中鉴定出169个上调基因和107个下调基因。预计所获得的基因列表包含对EPC功能和存活至关重要的关键基因,因此可能是体内识别EPC的潜在靶点,以及癌症和其他疾病中血管生成治疗性调节的靶点,在这些疾病中,新生血管生成起着关键作用。例如,该列表包括Syk和半乳糖凝集素-3,它们分别编码蛋白酪氨酸激酶和β-半乳糖苷结合蛋白,并且在EPCs中的表达高于三种对照内皮细胞。原位杂交显示,这些基因在小鼠发育的E11.5和E14.5阶段的胎肝分离细胞中表达。