小柯机器人

机械敏感的微动脉周围微环境可促进成骨和淋巴细胞生成
2021-02-27 23:56

美国德克萨斯大学西南医学中心Sean J. Morrison研究团队发现,机械敏感的微动脉周围微环境可促进成骨和淋巴细胞生成。相关论文于2021年2月24日在线发表在《自然》杂志上。

研究人员表示,表达瘦素受体(LEPR)的成年骨髓基质细胞是生长因子的关键来源,包括干细胞因子(SCF),被用于维持造血干细胞和早期限制性祖细胞。LEPR+细胞是异质性的,包括骨骼干细胞以及成骨和成脂祖细胞,尽管很少有标记可用于区分这些亚群或比较它们的功能。

研究人员发现,成骨生长因子osteolectin的表达将准备进行成骨的小动脉周围的LEPR+细胞与准备进行成脂的窦周间隙LEPR+细胞区分开(但保留了成骨的潜力)。微动脉周围的LEPR+osteolectin+细胞是迅速分裂、寿命短的成骨前体细胞,其在骨折后数量增加,并且在衰老过程中消耗。从osteolectin+细胞中敲除Scf不会影响造血干细胞或大多数限制性祖细胞的维持,但会耗尽普通淋巴祖细胞,损害淋巴细胞生成、细菌清除率以及急性细菌感染后的存活率。

微动脉周围的osteolectin+细胞维持需要机械刺激。奔跑能够增加微动脉周围的osteolectin+细胞常见淋巴祖细胞的频率。从osteolectin+细胞中敲除机械敏感性离子通道PIEZO1会减少osteolectin+细胞和骨淋巴样祖细胞。这些结果表明,骨髓中骨形成和淋巴细胞生成的这种尾动脉周围微环境通过机械刺激得以维持,并且在衰老过程中会耗尽。 

附:英文原文

Title: A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

Author: 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

Issue&Volume: 2021-02-24

Abstract: 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.

DOI: 10.1038/s41586-021-03298-5

Source: https://www.nature.com/articles/s41586-021-03298-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0