Arai Fumio, Hirao Atsushi, Ohmura Masako, Sato Hidetaka, Matsuoka Sahoko, Takubo Keiyo, Ito Keisuke, Koh Gou Young, Suda Toshio
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Cell. 2004 Jul 23;118(2):149-61. doi: 10.1016/j.cell.2004.07.004.
The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.
静止状态被认为是维持造血干细胞（HSC）不可或缺的特性。造血干细胞与其特定微环境（即干细胞龛）的相互作用对于骨髓（BM）中的成人造血至关重要。在此，我们证明表达受体酪氨酸激酶Tie2的造血干细胞处于静止且抗凋亡状态，并且构成造血干细胞的侧群（SP），其黏附于骨髓龛中的成骨细胞（OB）。Tie2与其配体血管生成素-1（Ang-1）的相互作用在体外诱导造血干细胞形成鹅卵石样集落，并在体内维持造血干细胞的长期重建造血活性。此外，Ang-1增强了造血干细胞进入静止状态的能力并诱导其黏附于骨，从而保护造血干细胞池免受骨髓抑制应激的影响。这些数据表明，Tie2/Ang-1信号通路在维持骨髓龛中造血干细胞的静止状态中起着关键作用。
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