Kubo Atsushi, Chen Vincent, Kennedy Marion, Zahradka Elizabeth, Daley George Q, Keller Gordon
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Blood. 2005 Jun 15;105(12):4590-7. doi: 10.1182/blood-2004-10-4137. Epub 2005 Feb 22.
In this report we have investigated the role of the homeobox gene Hex in the development and differentiation of the blast colony-forming cell (BL-CFC), a progenitor with hemangioblast characteristics generated in embryonic stem (ES) cell-derived embryoid bodies (EBs). Molecular analysis showed that Hex is expressed in mesoderm, in populations that contain BL-CFCs, and in blast cell colonies, the progeny of the BL-CFCs. Hex(-/-) EBs displayed a defect in macrophage development but generated higher numbers of BL-CFCs than did wild-type EBs. In addition to differences in these progenitor populations, we also found that endothelial cells from the Hex(-/-) EBs showed enhanced proliferative potential compared with those from wild-type EBs. Forced expression of Hex at the onset of ES cell differentiation resulted in reduced EB cellularity, fetal liver kinase-1 (Flk-1) expression, and BL-CFC development. Taken together, these findings demonstrate that Hex functions at multiple stages of development within the differentiating EBs and uncover a novel role for this transcription factor as a negative regulator of the hemangioblast and the endothelial lineage.
在本报告中，我们研究了同源框基因Hex在胚泡集落形成细胞（BL-CFC）的发育和分化中的作用，BL-CFC是一种在胚胎干细胞（ES）衍生的胚状体（EB）中产生的具有成血管细胞特征的祖细胞。分子分析表明，Hex在中胚层、含有BL-CFC的群体以及胚泡细胞集落（BL-CFC的后代）中表达。Hex基因敲除的EB在巨噬细胞发育方面存在缺陷，但产生的BL-CFC数量比野生型EB更多。除了这些祖细胞群体存在差异外，我们还发现，与野生型EB来源的内皮细胞相比，Hex基因敲除的EB来源的内皮细胞具有更强的增殖潜力。在ES细胞分化开始时强制表达Hex会导致EB细胞数量减少、胎儿肝激酶-1（Flk-1）表达降低以及BL-CFC发育受阻。综上所述，这些发现表明Hex在分化的EB的多个发育阶段发挥作用，并揭示了这种转录因子作为成血管细胞和内皮谱系的负调节因子的新作用。
