A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis.
A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis.
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DOI：
10.1038/s41586-021-03298-5
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Morrison SJ
中科院分区：
文献类型：
--
作者：
Shen B;Tasdogan A;Ubellacker JM;Zhang J;Nosyreva ED;Du L;Murphy MM;Hu S;Yi Y;Kara N;Liu X;Guela S;Jia Y;Ramesh V;Embree C;Mitchell EC;Zhao YC;Ju LA;Hu Z;Crane GM;Zhao Z;Syeda R;Morrison SJ
成人骨髓中的瘦素受体+（LepR+）基质细胞是用于维持造血干细胞（HSC）和早期限制性祖细胞的生长因子（包括干细胞因子（SCF））的关键来源。LepR+细胞是异质性的，包括骨骼干细胞、成骨祖细胞和成脂祖细胞，尽管很少有标记物可用于区分这些亚群或比较它们的功能。在这里，我们显示了成骨生长因子Osteolectin的表达，将准备进行成骨的动脉周围LepR+细胞与准备进行脂肪形成（但保留成骨潜力）的窦周LepR+细胞区分开来。小动脉周围LepR+Osteolectin+细胞是快速分裂、寿命短的成骨祖细胞，其在骨折后数量增加，并在老化过程中耗尽。从成人骨凝集素+细胞中删除Scf并不影响HSC或大多数限制性祖细胞的维持，但会耗尽常见的淋巴样祖细胞（CLP），损害淋巴细胞生成、细菌清除和急性细菌感染后的存活。动脉周围骨凝集素+细胞维持需要机械刺激。自主跑增加，而后肢卸载减少，动脉周围骨粘连蛋白+细胞和CLPs的频率。从Osteolectin+细胞中删除机械敏感性离子通道Piezo1，耗尽Osteolectin+细胞和CLP。骨髓中用于骨生成和淋巴细胞生成的动脉周围小生境通过机械刺激维持，并在衰老过程中耗尽。骨髓中用于骨生成和淋巴细胞生成的动脉周围小生境通过机械刺激维持，并在衰老过程中耗尽。
Leptin Receptor+ (LepR+) stromal cells in adult bone marrow are a critical source of growth factors, including Stem Cell Factor (SCF), for the maintenance of hematopoietic stem cells (HSCs) and early restricted progenitors. LepR+ cells are heterogeneous, including skeletal stem cells, osteogenic, and adipogenic progenitors, though few markers have been available to distinguish these subsets or to compare their functions. Here we show expression of an osteogenic growth factor, Osteolectin, 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 aging. Deletion of Scf from adult Osteolectin+ cells did not affect the maintenance of HSCs or most restricted progenitors but depleted common lymphoid progenitors (CLPs), impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar Osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, while hindlimb unloading decreased, the frequencies of peri-arteriolar Osteolectin+ cells and CLPs. Deletion of the mechanosensitive ion channel, Piezo1, from Osteolectin+ cells depleted Osteolectin+ cells and CLPs. A peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during aging. A peri-arteriolar niche in the bone marrow for osteogenesis and lymphopoiesis is maintained by mechanical stimulation and is depleted during aging.
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影响因子：
64.5
作者：
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通讯作者：
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