Perry John M, Harandi Omid F, Porayette Prashanth, Hegde Shailaja, Kannan Arun K, Paulson Robert F
Cell and Developmental Biology Option, Pennsylvania State University, University Park, PA 16802, USA.
Blood. 2009 Jan 22;113(4):911-8. doi: 10.1182/blood-2008-03-147892. Epub 2008 Oct 16.
The production of mature cells necessitates that lineage-committed progenitor cells be constantly generated from multipotential progenitors. In addition, the ability to respond rapidly to physiologic stresses requires that the signals that regulate the maintenance of progenitor populations be coordinated with the signals that promote differentiation of progenitors. Here we examine the signals that are necessary for the maintenance of the BMP4-dependent stress erythropoiesis pathway. Our previous work demonstrated that BMP4, stem cell factor, and hypoxia act in concert to promote the expansion of a specialized population of stress erythroid progenitors in the spleen during the recovery from acute anemia. Our analysis shows that acute anemia leads to an almost complete mobilization of BMP4-responsive stress erythroid burst-forming units; therefore, new stress progenitors must be recruited to the spleen to replenish this system. We show that bone marrow cells can home to the spleen and, in response to a signal in the spleen microenvironment, Hedgehog, they develop into BMP4-responsive stress progenitors. Hedgehog induces the expression of BMP4, and together these 2 signals are required for the development of BMP4-responsive stress progenitors. These data demonstrate that the interplay between these 2 signals is crucial for maintenance of this stress response pathway.
成熟细胞的产生需要从多能祖细胞不断生成定向分化的祖细胞。此外，快速响应生理应激的能力要求调节祖细胞群体维持的信号与促进祖细胞分化的信号相协调。在此，我们研究维持BMP4依赖性应激红细胞生成途径所必需的信号。我们之前的工作表明，BMP4、干细胞因子和缺氧协同作用，在急性贫血恢复过程中促进脾脏中一类特殊应激红系祖细胞的扩增。我们的分析表明，急性贫血导致几乎所有对BMP4有反应的应激红系爆式形成单位动员起来；因此，必须招募新的应激祖细胞到脾脏以补充这个系统。我们发现骨髓细胞可以归巢到脾脏，并在脾脏微环境中的信号刺猬信号蛋白（Hedgehog）作用下，发育成为对BMP4有反应的应激祖细胞。刺猬信号蛋白诱导BMP4的表达，这两个信号共同作用是对BMP4有反应的应激祖细胞发育所必需的。这些数据表明，这两个信号之间的相互作用对于维持这种应激反应途径至关重要。
