Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche
Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche
复制标题
DOI：
10.1016/j.stem.2007.10.020
复制
发表时间：
2007-12-01
期刊：
影响因子：
23.9
通讯作者：
Suda, Toshio
中科院分区：
文献类型：
--
作者：
Yoshihara, Hiroki;Arai, Fumio;Suda, Toshio
造血干细胞（hsc）的维持依赖于与其生态位的相互作用。在这里，我们发现表达血小板生成素（THPO）受体MPL的长期(LT)-造血干细胞在成人骨髓（BM）中是一个静止的群体，并且与产生THPO的成骨细胞密切相关。THPO/MPIL信号在造血干细胞中上调β 1-整合素和细胞周期蛋白依赖性激酶抑制剂。此外，抗MPL中和抗体AMM2和THPO处理对THPO/MPL通路的抑制和刺激显示出对LT-HSC静止的相互调节。AMM2处理减少了静止lt -HSC的数量，并允许外源HSC在没有照射的情况下植入。相比之下，外源性THPO在体内瞬间增加静止的HSC种群，随后诱导HSC增殖。总之，这些观察结果表明THPO/MPL信号在成骨细胞生态位的LT-HSC调节中起着关键作用。
Maintenance of hematopoietic stem cells (HSCs) depends on interaction with their niche. Here we show that the long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, MPL, are a quiescent population in adult bone marrow (BM) and are closely associated with THPO-producing osteoblastic cells. THPO/MPIL signaling upregulated beta 1-integrin and cyclin-dependent kinase inhibitors in HSCs. Furthermore, inhibition and stimulation of THPO/MPL pathway by treatments with anti-MPL neutralizing antibody, AMM2, and with THPO showed reciprocal regulation of quiescence of LT-HSC. AMM2 treatment reduced the number of quiescent LT-HSCs and allowed exogenous HSC engraftment without irradiation. By contrast, exogenous THPO transiently increased quiescent HSC population and subsequently induced HSC proliferation in vivo. Altogether, these observations suggest that THPO/MPL signaling plays a critical role of LT-HSC regulation in the osteoblastic niche.