Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche
Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche
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DOI：
10.1016/j.cell.2004.07.004
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发表时间：
2004-07-23
期刊：
影响因子：
64.5
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Arai, F;Hirao, A;Suda, T
静止状态被认为是维持造血干细胞(HSCs)不可或缺的特性。造血干细胞与其特定的微环境之间的相互作用，即所谓的干细胞微环境，对于成人骨髓(BM)的造血至关重要。在这里，我们证明了表达受体酪氨酸激酶Tie2的HSC是静止的和抗凋亡的，并且包括一个侧群(SP)的HSC，它们附着在BM利基中的成骨细胞(OB)上。Tie2与其配体血管生成素-1(Ang-1)相互作用，在体外诱导HSCs形成鹅卵石，并在体内维持HSCs的长期扩增活性。此外，Ang-1增强了HSC静止并诱导其与骨黏附的能力，从而保护HSC不受骨髓抑制压力的影响。这些数据表明，Tie2/Ang-1信号通路在维持骨髓间充质干细胞处于静止状态中起着关键作用。
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.