Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors
Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors
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DOI：
10.1172/jci41291
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发表时间：
2010-12-01
影响因子：
15.9
通讯作者：
Paulson, Robert F.
中科院分区：
文献类型：
--
作者：
Harandi, Omid F.;Hedge, Shailaja;Paulson, Robert F.
急性贫血应激诱导全身反应，旨在增加向缺氧组织的氧气输送。红细胞生成增加是这种反应的关键组成部分。急性贫血的恢复依赖于应激性红细胞生成，这与稳态红细胞生成不同。在这项研究中，我们发现骨形态发生蛋白4依赖性（BMP 4依赖性）应激红细胞生成途径是骨髓移植后红细胞短期辐射防护所必需的和特异性的。BMP 4信号促进了三种应激红系祖细胞群体的发育，这些祖细胞在小鼠骨髓移植后在脾脏中扩增。这些祖细胞不对应于先前确定的骨髓稳态祖细胞。最不成熟的人口的压力祖细胞能够自我更新，同时保持红细胞生成没有贡献的其他谱系时，连续移植到辐照的第二和第三受体。这些数据表明，在移植后立即期间，脾脏的微环境被改变，这使得供体骨髓细胞采取应激红细胞生成的命运，并促进应激红系祖细胞的快速扩增和分化。我们的研究结果还表明，应激性红细胞生成可能通过靶向BMP 4信号通路来操纵，以改善损伤后的存活率。
Acute anemic stress induces a systemic response designed to increase oxygen delivery to hypoxic tissues. Increased erythropoiesis is a key component of this response. Recovery from acute anemia relies on stress erythropoiesis, which is distinct from steady-state erythropoiesis. In this study we found that the bone morphogenetic protein 4-dependent (BMP4-dependent) stress erythropoiesis pathway was required and specific for erythroid short-term radioprotection following bone marrow transplantation. BMP4 signaling promoted the development of three populations of stress erythroid progenitors, which expanded in the spleen subsequent to bone marrow transplantation in mice. These progenitors did not correspond to previously identified bone marrow steady-state progenitors. The most immature population of stress progenitors was capable of self renewal while maintaining erythropoiesis without contribution to other lineages when serially transplanted into irradiated secondary and tertiary recipients. These data suggest that during the immediate posttransplant period, the microenvironment of the spleen is altered, which allows donor bone marrow cells to adopt a stress erythropoietic fate and promotes the rapid expansion and differentiation of stress erythroid progenitors. Our results also suggest that stress erythropoiesis may be manipulated through targeting the BMP4 signaling pathway to improve survival after injury.