Perry John M, Harandi Omid F, Paulson Robert F
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Blood. 2007 May 15;109(10):4494-502. doi: 10.1182/blood-2006-04-016154. Epub 2007 Feb 6.
The erythroid response to acute anemia relies on the rapid expansion in the spleen of a specialized population of erythroid progenitors termed stress BFU-E. This expansion requires BMP4/Madh5-dependent signaling in vivo; however, in vitro, BMP4 alone cannot recapitulate the expansion of stress BFU-E observed in vivo, which suggests that other signals are required. In this report we show that mutation of the Kit receptor results in a severe defect in the expansion of stress BFU-E, indicating a role for the Kit/SCF signaling pathway in stress erythropoiesis. In vitro analysis showed that BMP4 and SCF are necessary for the expansion of stress BFU-E, but only when spleen cells were cultured in BMP4 + SCF at low-oxygen concentrations did we recapitulate the expansion of stress BFU-E observed in vivo. Culturing spleen cells in BMP4, SCF under hypoxic conditions resulted in the preferential expansion of erythroid progenitors characterized by the expression of Kit, CD71, and TER119. This expression pattern is also seen in stress erythroid progenitors isolated from patients with sickle cell anemia and patients with beta-thalassemia. Taken together these data demonstrate that SCF and hypoxia synergize with BMP4 to promote the expansion and differentiation of stress BFU-E during the recovery from acute anemia.
红系对急性贫血的反应依赖于一种称为应激性爆式红系集落形成单位（stress BFU-E）的红系祖细胞特殊群体在脾脏中的快速扩增。这种扩增在体内需要骨形态发生蛋白4（BMP4）/ Mothers against decapentaplegic homolog 5（Madh5）依赖性信号传导；然而，在体外，单独的BMP4不能重现体内观察到的应激性BFU-E的扩增，这表明还需要其他信号。在本报告中，我们表明Kit受体的突变导致应激性BFU-E扩增出现严重缺陷，表明Kit/干细胞因子（SCF）信号通路在应激性红细胞生成中起作用。体外分析表明，BMP4和SCF是应激性BFU-E扩增所必需的，但只有当脾细胞在低氧浓度下于BMP4 + SCF中培养时，我们才能重现体内观察到的应激性BFU-E的扩增。在缺氧条件下于BMP4、SCF中培养脾细胞导致以Kit、CD71和TER119表达为特征的红系祖细胞优先扩增。这种表达模式在从镰状细胞贫血患者和β地中海贫血患者中分离出的应激性红系祖细胞中也可见。综上所述，这些数据表明，SCF和缺氧与BMP4协同作用，以促进急性贫血恢复过程中应激性BFU-E的扩增和分化。
