Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment
Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment
复制标题
DOI：
10.1016/j.cell.2007.03.055
复制
发表时间：
2007-06-15
期刊：
影响因子：
64.5
通讯作者：
Orkin, Stuart H.
中科院分区：
文献类型：
--
作者：
Walkley, Carl R.;Shea, Jeremy M.;Orkin, Stuart H.
造血是由干细胞(HSCs)维持的，干细胞通过整合内在和外在信号来决定命运，后者来自骨髓(BM)微环境。细胞周期调控可以调节干细胞的命运，但目前尚不清楚这是命运决定的内在还是外在影响因素。我们研究了视网膜母细胞瘤蛋白(RB)在造血中的作用，RB是细胞周期的中心调节因子。Rb在小鼠造血系统中的广泛失活导致了严重的骨髓增殖。骨髓间充质干细胞由于移位至髓外部位和分化而丢失。这种表型不是HSCs固有的，而是髓系细胞和微环境之间依赖Rb的相互作用的结果。这些发现表明，骨髓增殖可能是造血细胞和壁龛之间相互干扰的结果。因此，RB通过维持骨髓支持正常造血和HSCs的能力，对HSCs进行外在调节。
Hematopoiesis is maintained by stem cells (HSCs) that undergo fate decisions by integrating intrinsic and extrinsic signals, with the latter derived from the bone marrow (BM) microenvironment. Cell-cycle regulation can modulate stem cell fate, but it is unknown whether this represents an intrinsic or extrinsic effector of fate decisions. We have investigated the role of the retinoblastoma protein (RB), a central regulator of the cell cycle, in hematopoiesis. Widespread inactivation of RB in the murine hematopoietic system resulted in profound myeloproliferation. HSCs were lost from the BM due to mobilization to extramedullary sites and differentiation. This phenotype was not intrinsic to HSCs, but, rather, was the consequence of an RB-dependent interaction between myeloid-derived cells and the microenvironment. These findings demonstrate that myeloproliferation may result from perturbed interactions between hematopoietic cells and the niche. Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and HSCs.