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A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis
Nature ( IF 50.5 ) Pub Date : 2021-02-24 , DOI: 10.1038/s41586-021-03298-5
Bo Shen 1 , Alpaslan Tasdogan 1 , Jessalyn M Ubellacker 1 , Jingzhu Zhang 1 , Elena D Nosyreva 2 , Liming Du 1 , Malea M Murphy 1 , Shuiqing Hu 3 , Yating Yi 4 , Nergis Kara 1 , Xin Liu 1 , Shay Guela 1 , Yuemeng Jia 1 , Vijayashree Ramesh 1 , Claire Embree 1 , Evann C Mitchell 1 , Yunduo C Zhao 5 , Lining A Ju 5 , Zhao Hu 5 , Genevieve M Crane 6 , Zhiyu Zhao 1 , Ruhma Syeda 3 , Sean J Morrison 1, 7
Affiliation  

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 progenitors1,2,3,4,5,6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7,8,9,10,11,12, 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, osteolectin13,14, 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.



中文翻译:

用于成骨和淋巴细胞生成的机械敏感的小动脉周围生态位

成人骨髓中表达瘦素受体 (LEPR) 的基质细胞是生长因子的重要来源,包括干细胞因子 (SCF),用于维持造血干细胞和早期受限祖细胞1,2,3,4,5, 6 . LEPR +细胞是异质的,包括骨骼干细胞和成骨和脂肪祖细胞7,8,9,10,11,12,尽管很少有标记可用于区分这些亚群或比较它们的功能。在这里,我们显示成骨生长因子骨凝集素13,14的表达将准备接受成骨的小动脉周围LEPR +细胞与窦周 LEPR +区分开来准备进行脂肪生成的细胞(但保留成骨潜力)。小动脉周围的LEPR +骨凝集素+细胞是快速分裂的短寿命成骨祖细胞,它们在骨折后数量增加,并在衰老过程中耗尽。从成人骨凝集素+细胞中删除Scf不影响造血干细胞或大多数受限祖细胞的维持,但会耗尽常见的淋巴祖细胞,损害淋巴细胞生成、细菌清除和急性细菌感染后的存活。小动脉周围骨凝集素+细胞维持需要机械刺激。自主跑步增加,而后肢卸载减少,小动脉周围骨凝集素的频率+细胞和常见的淋巴祖细胞。从骨凝集素+细胞中删除机械敏感性离子通道 PIEZO1 会耗尽骨凝集素+细胞和常见的淋巴祖细胞。这些结果表明,骨髓中用于骨生成和淋巴细胞生成的小动脉周围生态位通过机械刺激得以维持,并在衰老过程中耗尽。

更新日期:2021-02-24
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