A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

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.