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首页> 外文期刊>Nature >Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis
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Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis

机译：骨髓祖细胞簇的形成驱动紧急和白血病骨髓生成

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摘要

Although many aspects of blood production are well understood, the spatial organization of myeloid differentiation in the bone marrow remains unknown. Here we use imaging to track granulocyte/macrophage progenitor (GMP) behaviour in mice during emergency and leukaemic myelopoiesis. In the steady state, we find individual GMPs scattered throughout the bone marrow. During regeneration, we observe expanding GMP patches forming defined GMP clusters, which, in turn, locally differentiate into granulocytes. The timed release of important bone marrow niche signals (SCF, IL-1 beta, G-CSF, TGF beta and CXCL4) and activation of an inducible Irf8 and beta-catenin progenitor self-renewal network control the transient formation of regenerating GMP clusters. In leukaemia, we show that GMP clusters are constantly produced owing to persistent activation of the self-renewal network and a lack of termination cytokines that normally restore haematopoietic stem-cell quiescence. Our results uncover a previously unrecognized dynamic behaviour of GMPs in situ, which tunes emergency myelopoiesis and is hijacked in leukaemia.
机译：尽管血液生产的许多方面已广为人知，但骨髓中骨髓分化的空间组织仍然未知。在这里，我们使用成像来跟踪紧急情况和白血病骨髓生成过程中小鼠的粒细胞/巨噬细胞祖细胞（GMP）行为。在稳定状态下，我们发现单个GMP散布在整个骨髓中。在再生过程中，我们观察到扩展的GMP斑块形成了定义的GMP簇，而这些簇又局部分化为粒细胞。重要的骨髓生态位信号（SCF，IL-1 beta，G-CSF，TGF beta和CXCL4）的定时释放以及诱导型Irf8和β-catenin祖细胞自我更新网络的激活控制着再生GMP簇的瞬时形成。在白血病中，我们显示由于持续不断的自我更新网络激活和缺乏通常恢复造血干细胞静止状态的终止细胞因子而不断产生的GMP簇。我们的研究结果揭示了原先无法识别的GMP的动态行为，该行为可调节紧急骨髓细胞生成并被白血病所劫持。

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  • 来源
    《Nature》 |2017年第7648期|53-58|共6页
  • 作者

    Herault Aurelie; Binnewies Mikhail; Leong Stephanie; Calero-Nieto Fernando; Zhang Si Yi; Kang Yoon-A; Wang Xiaonan; Pietras Eric M.; Chu S. Haihua; Barry-Holson Keegan; Armstrong Scott; Gottgens Berthold; Passegue Emmanuelle;

  • 作者单位

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Wellcome Trust & MRC Cambridge Stem Cell Inst, Hills Rd, Cambridge CB2 0XY, England;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Wellcome Trust & MRC Cambridge Stem Cell Inst, Hills Rd, Cambridge CB2 0XY, England;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Harvard Med Sch, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA|Harvard Med Sch, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA;

    Harvard Med Sch, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA|Harvard Med Sch, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA;

    Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Wellcome Trust & MRC Cambridge Stem Cell Inst, Hills Rd, Cambridge CB2 0XY, England;

    Univ Calif San Francisco, Div Hematol Oncol, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA|Columbia Univ, Med Ctr, Dept Genet & Dev, Columbia Stem Cell Initiat, New York, NY 10032 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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