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Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation

机译：活性氧使果蝇造血祖细胞分化

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摘要

Reactive oxygen species (ROS), produced during various electron transfer reactions in vivo, are generally considered to be deleterious to cells. In the mammalian haematopoietic system, haematopoietic stem cells contain low levels of ROS. However, unexpectedly, the common myeloid progenitors (CMPs) produce significantly increased levels of ROS. The functional significance of this difference in ROS level in the two progenitor types remains unresolved. Here we show that Drosophila multipotent haematopoietic progenitors, which are largely akin to the mammalian myeloid progenitors, display increased levels of ROS under in vivo physiological conditions, which are downregulated on differentiation. Scavenging the ROS from these haematopoietic progenitors by using in vivo genetic tools retards their differentiation into mature blood cells. Conversely, increasing the haematopoietic progenitor ROS beyond their basal level triggers precocious differentiation into all three mature blood cell types found in Drosophila, through a signalling pathway that involves JNK and FoxO activation as well as Polycomb downregulation. We conclude that the developmentally regulated, moderately high ROS level in the progenitor population sensitizes them to differentiation, andrnestablishes a signalling role for ROS in the regulation of haematopoietic cell fate. Our results lead to a model that could be extended to reveal a probable signalling role for ROS in the differentiation of CMPs in mammalian haematopoietic development and oxidative stress response.
机译：在体内各种电子转移反应过程中产生的活性氧（ROS）通常被认为对细胞有害。在哺乳动物的造血系统中，造血干细胞含有低水平的ROS。但是，出乎意料的是，常见的骨髓祖细胞（CMP）产生的ROS水平显着增加。两种祖细胞中ROS水平差异的功能意义仍未解决。在这里，我们显示果蝇多能性造血祖细胞，很大程度上类似于哺乳动物的髓祖细胞，显示出在体内生理条件下ROS水平升高，其在分化时被下调。通过使用体内遗传工具清除这些造血祖细胞中的ROS，可阻止其分化为成熟血细胞。相反，通过涉及JNK和FoxO激活以及Polycomb下调的信号通路，使造血祖细胞ROS超过其基础水平会触发早熟分化为果蝇中发现的所有三种成熟血细胞类型。我们得出的结论是，祖细胞中受发育调节的中等水平的ROS水平使它们对分化敏感，并建立了ROS在造血细胞命运调控中的信号传导作用。我们的结果导致了一个模型，该模型可以扩展以揭示ROS在哺乳动物造血发育和氧化应激反应中CMP分化中的可能信号作用。

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  • 来源
    《Nature》 |2009年第24期|537-541|共5页
  • 作者

    Edward Owusu-Ansah; Utpal Banerjee;

  • 作者单位

    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA Molecular Biology Institute, University of California, Los Angeles, California 90095, USA Department of Biologicai Chemistry, University of California, Los Angeles, California 90095, USA Eliand Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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