Genetic marking of hematopoietic stem and endothelial cells:: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain
Genetic marking of hematopoietic stem and endothelial cells:: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain
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DOI：
10.1182/blood-2005-09-3747
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发表时间：
2006-06-01
期刊：
影响因子：
20.3
通讯作者：
Nakauchi, Hiromitsu
中科院分区：
文献类型：
--
作者：
Takayanagi, Shin-ichiro;Hiroyarna, Takashi;Nakauchi, Hiromitsu
使用计算机数据库搜索，我们确定了一个新的基因编码的细胞表面分子与血小板反应蛋白结构域，并指定为跨膜分子与血小板反应蛋白模块（Tmtsp）的基因。使用特异性单克隆抗体和Venus（Tmtsp基因座中黄色荧光蛋白敲入小鼠的变体）对Tmtsp进行表达谱分析，证明其在造血和内皮细胞中特异性表达。在淋巴造血细胞中，Tmtsp主要在造血干细胞和祖细胞中表达，并且表达水平随着细胞分化而逐渐下降。Venus的表达忠实地追踪了Tmtsp的表达，并且Venus的表达水平与体外造血活性以及体内骨髓重建能力良好相关。值得注意的是，Venus的表达标志着胚胎外卵黄囊和胚胎内卵黄囊-性腺-中肾（AGM）区域中永久性造血的发育，并且与CD 41结合，显著促进了胚胎第10.5天（E10.5）CD 41（+）Venus（高）组分中发育祖细胞的富集。在这种情况下，Tmtsp是一种新的标记基因的原始造血细胞和内皮细胞，和Tmtsp（金星/+）小鼠将作为一个有价值的小鼠模型，胚胎和成人造血分析，以及血管生物学。
Using an in silico database search, we identified a novel gene encoding a cell surface molecule with a thrombospondin domain, and designated the gene as transmembrane molecule with thrombospondin module (Tmtsp). Expression profiling of Tmtsp using specific monoclonal antibodies and Venus, a variant of yellow fluorescent protein knock-in mice in the Tmtsp locus, demonstrated its specific expression in hematopoietic and endothelial cells. In lymphohematopoietic cells, Tmtsp was predominantly expressed in hematopoietic stem and progenitor cells, and the level of expression gradually declined as the cells differentiated. Venus expression faithfully traced the expression of Tmtsp, and the level of Venus expression correlated well to the in vitro hematopoietic activity as well as the in vivo bone marrow repopulating capacity. Notably, Venus expression marked the development of definitive hematopoiesis in both the extraembryonic yolk sac and the intraembryonic aorta-gonad-mesonephros (AGM) region and, in combination with CD41, strikingly promoted the enrichment of developing progenitors in the CD41(+)Venus(high) fraction at embryonic day 10.5 (E10.5). In this context, Tmtsp is a novel marker gene for primitive hematopoietic cells and endothelial cells, and Tmtsp(Venus/+) mice would serve as a valuable mouse model for the analysis of both embryonic and adult hematopoiesis, as well as for vascular biology.