A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

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 and Sean J. Morrison ()
Additional contact information
Bo Shen: University of Texas Southwestern Medical Center
Alpaslan Tasdogan: University of Texas Southwestern Medical Center
Jessalyn M. Ubellacker: University of Texas Southwestern Medical Center
Jingzhu Zhang: University of Texas Southwestern Medical Center
Elena D. Nosyreva: University of Texas Southwestern Medical Center
Liming Du: University of Texas Southwestern Medical Center
Malea M. Murphy: University of Texas Southwestern Medical Center
Shuiqing Hu: University of Texas Southwestern Medical Center
Yating Yi: School of Dentistry, Texas A&M University
Nergis Kara: University of Texas Southwestern Medical Center
Xin Liu: University of Texas Southwestern Medical Center
Shay Guela: University of Texas Southwestern Medical Center
Yuemeng Jia: University of Texas Southwestern Medical Center
Vijayashree Ramesh: University of Texas Southwestern Medical Center
Claire Embree: University of Texas Southwestern Medical Center
Evann C. Mitchell: University of Texas Southwestern Medical Center
Yunduo C. Zhao: The University of Sydney
Lining A. Ju: The University of Sydney
Zhao Hu: The University of Sydney
Genevieve M. Crane: Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic
Zhiyu Zhao: University of Texas Southwestern Medical Center
Ruhma Syeda: University of Texas Southwestern Medical Center
Sean J. Morrison: University of Texas Southwestern Medical Center

Nature, 2021, vol. 591, issue 7850, 438-444

Abstract: 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 progenitors1–6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7–12, 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.

Date: 2021
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DOI: 10.1038/s41586-021-03298-5

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