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A mechanosensiti ve peri-arteriolar niche for osteogenesis and lymphopoiesis

机译：骨质发生和淋巴细胞症的机械肌肉

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摘要

Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors~(1-6). LEPR~(+)cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors~(7-12), although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin~(13,14), distinguishes peri-arteriolar LEPR~(+)cells poised to undergo osteogenesis from peri-sinusoidal LEPR~(+)cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR~(+)osteolectin~(+)cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin~(+)cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin~(+)cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin~(+)cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin~(+)cells depleted osteolectin~(+)cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing.
机译：表达瘦蛋白受体（LEPR）的成年骨髓中的基质细胞是生长因子的临界来源，包括干细胞因子（SCF），用于维持出血血管干细胞和早期受限制的祖细胞〜（1-6）。 LePR〜（+）细胞是异质的，包括骨骼干细胞和骨质发生和脂肪发生祖母〜（7-12），但是有很少的标记可用于区分这些子集或比较它们的功能。在这里，我们表明，骨素生长因子，骨胶蛋白〜（13,14）的表达，区分Peri-arteriolar的Lepr〜（+）细胞从Peri-sinusoidal Lepr〜（+）细胞进行骨质发生，使其进行讨论（但保留osteogenic潜力）。 Peri-arteriolar Lepr〜（+）骨胶蛋白〜（+）细胞正在迅速分裂，短暂的骨质成骨祖细胞，在骨折后的数量增加并在老化期间耗尽。缺失来自成人骨胶蛋白〜（+）细胞的SCF不影响血液吞噬干细胞或最受限制的祖细胞的维持，但含有常见的淋巴祖细胞，淋巴缺血，细菌间隙损害，急性细菌感染后存活。 Peri-arteriolar骨胶蛋白〜（+）细胞维持所需的机械刺激。自愿运行增加，而后肢卸载减少，腹膜血栓素〜（+）细胞和常见淋巴祖细胞的频率。从骨屈虑菌素〜（+）细胞的机械敏感性离子通道压电1缺乏骨细胞素〜（+）细胞和常见淋巴祖细胞。这些结果表明，通过机械刺激和老化期间耗尽骨髓中骨髓内发生和淋巴卵泡的Peri-arteriolar Niche。

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  • 来源
    《Nature》 |2021年第7850期|438-444|共7页
  • 作者

    Bo Shen; Alpaslan Tasdogan; Jessalyn M Ubellacker; Jingzhu Zhang; Elena D Nosyreva; Liming Du; Malea M Murphy; Shuiqing Hu; Yating Yi; Nergis Kara; Xin Liu; Shay Guela; Yuemeng Jia; Vijayashree Ramesh; Claire Embree; Evann C Mitchell; Yunduo C Zhao; Lining A Ju; Zhao Hu; Genevieve M Crane; Zhiyu Zhao; Ruhma Syeda; Sean J Morrison;

  • 作者单位

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Department of Neuroscience University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Department of Molecular Biology University of Texas Southwestern Medical Center;

    Department of Restorative Sciences School of Dentistry Texas A&M University;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    School of Biomedical Engineering Heart Research Institute and Charles Perkins Center The University of Sydney;

    School of Biomedical Engineering Heart Research Institute and Charles Perkins Center The University of Sydney;

    School of Biomedical Engineering Heart Research Institute and Charles Perkins Center The University of Sydney;

    Robert J. Tomsich Pathology & Laboratory Medicine Institute Cleveland Clinic;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center;

    Department of Molecular Biology University of Texas Southwestern Medical Center;

    Children's Research Institute and the Department of Pediatrics University of Texas Southwestern Medical Center|Howard Hughes Medical Institute University of Texas Southwestern Medical Center;

  • 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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