Transdifferentiation of hematopoietic stem cells and endothelial progenitors

在本项目中，我们试图阐明从普通祖细胞或血管母细胞向造血干细胞(HSCs)和血管内皮细胞分化的途径。胚胎的背主动脉内有血源性内皮细胞的存在，而成人骨髓中的血管母细胞尚未在克隆水平上被明确。造血干细胞和血管内皮细胞都表达共同的表面分子CD31、CD34、Flk-1和血管生成素受体Tie2。1)我们已经证明Tie2阳性的HSC与产生Ang-1的成骨细胞黏附，并且这个信号对维持静止的干细胞至关重要(Cell，2004)。2)血管生成素样蛋白(Angptl)1和2协同发挥抗血管内皮细胞凋亡的作用。Angptl 6 KO小鼠表现出肥胖，而TG小鼠表现出对肥胖和糖尿病的一些抵抗力(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).