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Haematopoietic stem cells depend on Gα_s-mediated signalling to engraft bone marrow

机译:造血干细胞依赖于Gα_s介导的信号植入骨髓

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摘要

Haematopoietic stem and progenitor cells (HSPCs) change location during development and circulate in mammals throughout life, moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory a subunit (Gα_s). HSPCs from adult mice deficient in Gα_s (Gα_s~(-/-)) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow micro-vasculature. If deleted after engraftment, Gα_s deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of Gα_s affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. Gα_s governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency.
机译:造血干细胞和祖细胞(HSPC)在发育过程中改变位置,并在整个生命中在哺乳动物中循环,移入和移出血液,在归巢,植入和保留的连续步骤中与骨髓engage接合,此处我们证明了HSPC植入了骨髓胎儿的发育取决于鸟嘌呤核苷酸结合蛋白刺激的一个亚基(Gα_s)。来自缺乏Gα_s(Gα_s〜(-/-))的成年小鼠的HSPC分化并经历趋化作用,但也没有成年小鼠的骨髓归巢或移植到骨髓中,并且显示出无法参与骨髓微脉管系统。如果在植入后缺失,则Gα_s缺乏症不会导致缺乏在骨髓中的滞留,而是损害了细胞因子诱导的血液动员。为了测试Gα_s的激活是否影响HSPC,药理激活剂增强了体内的归巢和植入。 Gα_s控制体内生理条件下HSPC定位的特定方面,并且可能在药理学上针对提高移植效率。

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  • 来源
    《Nature》 |2009年第7243期|103-107|共5页
  • 作者单位

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA (G.B.A.) Department of Bioengineering, Graduate Schools of Engineering and Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan (U.-i.C);

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA;

    Endocrine Unit and Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA (G.B.A.) Department of Bioengineering, Graduate Schools of Engineering and Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan (U.-i.C);

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA;

    National Institute for Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA;

    National Institute for Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA;

    Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA;

    Endocrine Unit and Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, 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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