Transdifferentiation of hematopoietic stem cells and endothelial progenitors

本课题试图阐明造血干细胞和血管内皮细胞的分化途径。在胚胎的背主动脉中存在生血内皮细胞，而在成人骨髓中尚未明确成血管细胞的克隆水平。HSC和内皮细胞都表达共同的表面分子，CD 31，CD 34，Flk-1和Tie 2，Tie 2是血管生成素（Angs）的受体。1）我们已经证明Tie 2阳性的HSC粘附于产生Ang-1的成骨细胞，并且该信号对于维持静止的干细胞是至关重要的（Cell，2004）。2）血管生成素样蛋白（Angptl）1和2在斑马鱼中使用吗啉代协同显示对血管内皮细胞的抗凋亡作用。3）令人惊讶的是，Angptl 6参与能量代谢以及血管生成。Angptl 6 KO小鼠显示肥胖，而Tg小鼠显示对肥胖和糖尿病的一些抗性（Nat.Med.2005）。

In this project, we try to clarify the differentiation pathway to hematopoietic stem cells (HSCs) and vascular endothelial cells from common progenitor cells or hemangioblasts. Hemogenic endothelial cells were defined in dorsal aorta in embryos, while hemangioblasts were not clarified yet at a clonal level in adult bone marrow. Both HSCs and endothelial cells express common surface molecules, CD31, CD34, Flk-1 and Tie2, which is a receptor for angiopoietins (Angs).1)We have demonstrated that Tie2-positive HSCs adhere to Ang-1-producing osteoblasts, and that this signal is critical for maintaining the quiescent stem cells (Cell, 2004).2)Angiopoietin-like proteins (Angptl) 1 and 2 synergistically show the anti-apoptotic effects on vascular endothelial cells using a Morpholino in Zebrafish.3)Surprisingly, Angplt 6 is involved in the energy metabolism as well as angiogenesis. Angptl 6 KO mice show the obesity, while Tg mice show some resistance to obesity and diabetes (Nat.Med.2005).