Kim Dae Joong, Park Chun Shik, Yoon Jeong Kyo, Song Woo Keun
Department of Life Science and Molecular Disease Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea.
Cell Biochem Funct. 2008 Jan-Feb;26(1):24-32. doi: 10.1002/cbf.1391.
Embryonic stem (ES) cells have the potential to develop into various cell lineages including hemangioblasts (Flk1+), a common progenitor for hematopoietic and vascular endothelial cells. Previous studies indicate that Flk1+ cells, a marker for hemangioblast, can be derived from ES cell and that Flk1+ can be differentiated into hematopoietic or endothelial cells depending on culture conditions. We developed an improved in vitro system to generate Flk1+-enriched cultures from mouse ES cells and used this in vitro system to study the role of Wnt signalling in early endothelial progenitor cells. We determined the expression of the Wnt and Frizzled genes in Flk1+ cells derived from mouse ES cells. RT-PCR analyses identified significantly higher expression of non-canonical Wnt5a and Wnt11 genes in Flk1+ cells compared to Flk1- cells. In contrast, expression of canonical Wnt3a gene was reduced in Flk1+ cells. In addition, Frizzled2, Frizzled5 and Frizzled7 genes were also expressed at a higher level in Flk1+ cells. The differential expression of Wnt and Frizzled genes in Flk1+ cells provides a novel insight into the role of non-canonical Wnt signalling in vascular endothelial fate determination.
胚胎干细胞（ES细胞）有潜力发育成包括成血管细胞（Flk1+）在内的各种细胞谱系，成血管细胞是造血细胞和血管内皮细胞的共同祖细胞。先前的研究表明，作为成血管细胞标志物的Flk1+细胞可源自ES细胞，并且根据培养条件，Flk1+细胞可分化为造血细胞或内皮细胞。我们开发了一种改进的体外系统，从小鼠ES细胞中生成富含Flk1+的培养物，并利用该体外系统研究Wnt信号通路在早期内皮祖细胞中的作用。我们测定了从小鼠ES细胞衍生的Flk1+细胞中Wnt和卷曲蛋白基因的表达。逆转录聚合酶链反应（RT-PCR）分析表明，与Flk1-细胞相比，Flk1+细胞中非经典Wnt5a和Wnt11基因的表达显著更高。相反，经典Wnt3a基因在Flk1+细胞中的表达降低。此外，卷曲蛋白2、卷曲蛋白5和卷曲蛋白7基因在Flk1+细胞中的表达水平也更高。Flk1+细胞中Wnt和卷曲蛋白基因的差异表达为非经典Wnt信号通路在血管内皮细胞命运决定中的作用提供了新的见解。
