Stress erythropoiesis: new signals and new stress progenitor cells.
Stress erythropoiesis: new signals and new stress progenitor cells.
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压力红细胞生成：新信号和新的应激祖细胞。
DOI：
10.1097/moh.0b013e32834521c8
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发表时间：
2011-05
影响因子：
3.2
通讯作者：
Wu DC
中科院分区：
文献类型：
--
作者：
Paulson RF;Shi L;Wu DC
急性贫血应激诱导生理反应，包括新红细胞的快速发育。该过程被称为应激红细胞生成，其不同于稳态红细胞生成。我们对应激性红细胞生成的了解大部分来自对小鼠模型的分析。在这篇综述中，我们将讨论我们目前对调节小鼠应激红细胞生成的机制的理解，并讨论该领域的突出问题。应激性红细胞生成发生在小鼠脾脏、胎肝和成体肝脏中。调节这一过程的信号是Hedgehog，骨形态发生蛋白4（BMP 4），干细胞因子和缺氧。最近的研究结果表明，应激红细胞生成利用红细胞限制性自我更新应激祖细胞群体。虽然BMP 4依赖性应激红细胞生成途径首先在从急性贫血恢复期间表征，但对慢性贫血小鼠模型的分析表明，BMP 4依赖性应激红细胞生成途径的激活也响应于慢性贫血提供代偿性红细胞生成。BMP 4依赖性应激红细胞生成途径在从急性贫血中恢复中起关键作用，并且新的数据显示该途径补偿慢性贫血的鼠模型中无效的稳态红细胞生成。在小鼠中鉴定应激红系祖细胞的自我更新群体表明，对该途径的治疗操作可能对治疗人类贫血有用。然而，新疗法的开发将等待人类类似途径的表征。
Acute anemic stress induces a physiological response that includes the rapid development of new erythrocytes. This process is referred to as stress erythropoiesis, which is distinct from steady state erythropoiesis. Much of what we know about stress erythropoiesis comes from the analysis of murine models. In this review, we will discuss our current understanding of the mechanisms that regulate stress erythropoiesis in mice and discuss outstanding questions in the field. Stress erythropoiesis occurs in the murine spleen, fetal liver and adult liver. The signals that regulate this process are Hedgehog, bone morphogenetic protein 4 (BMP4), stem cell factor and hypoxia. Recent findings show that stress erythropoiesis utilizes a population of erythroid-restricted self-renewing stress progenitors. Although the BMP4-dependent stress erythropoiesis pathway was first characterized during the recovery from acute anemia, analysis of a mouse model of chronic anemia demonstrated that activation of the BMP4-dependent stress erythropoiesis pathway provides compensatory erythropoiesis in response to chronic anemia as well. The BMP4-dependent stress erythropoiesis pathway plays a key role in the recovery from acute anemia and new data show that this pathway compensates for ineffective steady state erythropoiesis in a murine model of chronic anemia. The identification of a self-renewing population of stress erythroid progenitors in mice suggests that therapeutic manipulation of this pathway may be useful for the treatment of human anemia. However, the development of new therapies will await the characterization of an analogous pathway in humans.