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Arteriolar niches maintain haematopoietic stem cell quiescence

机译：小动脉ni维持造血干细胞的静止

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摘要

Paul Frenette及同事采用"全标本共焦免疫荧 光成像和计算模拟''方法对造血干细胞(HSC) 细胞龛内不同细胞类型的空间分布进行了研 究。他们发现，静止的HSC专门与优先在"骨 内骨髓"中发现的小动脉关联，这些小动脉是 保持HSC静止所必需的。因此这些结果表明， 不同的HSC细胞龛(静止的或增殖性的）是由不 同血管类型所赋予的。%Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)~+ pericytes, distinct from sinusoid-associated leptin receptor (LEPR)~+ cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2~+ periarteriolar niches to LEPR~+ perisinusoidal niches. Conditional depletion of NG2~+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for mamtaining HSC quiescence.
机译：Paul Frenette及同事采用"全标本共焦免疫荧 光成像和计算模拟''方法对造血干细胞(HSC) 细胞龛内不同细胞类型的空间分布进行了研 究。他们发现，静止的HSC专门与优先在"骨 内骨髓"中发现的小动脉关联，这些小动脉是 保持HSC静止所必需的。因此这些结果表明， 不同的HSC细胞龛(静止的或增殖性的）是由不 同血管类型所赋予的。%Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)~+ pericytes, distinct from sinusoid-associated leptin receptor (LEPR)~+ cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2~+ periarteriolar niches to LEPR~+ perisinusoidal niches. Conditional depletion of NG2~+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for mamtaining HSC quiescence.

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  • 来源
    《Nature》 |2013年第7473期|637-643a1|共8页
  • 作者

    Yuya Kunisaki; Ingmar Brans; Christoph Scheiermann; Jalal Ahmed; Sandra Pinho; Dachuan Zhang; Toshihide Mizoguchi; Qiaozhi Wei; Daniel Lucas; Keisuke Ito; Jessica C. Mar; Aviv Bergman; Paul S. Frenette;

  • 作者单位

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Diisseldorf 40225, Germany;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Mount Sinai School of Medicine, New York, New York 10029, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA　WalterBrendel-Centre of Experimental Medicine, Ludwig-Maximilians-Universitat, Munchen, Munich 81377, Germany;

    Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA,Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, 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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