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.

Automated summary

Stromal cells in adult bone marrow expressing leptin receptor are a critical source of growth factors for haematopoietic stem cells. Among these cells, those expressing osteogenic growth factor osteolectin are poised for osteogenesis, while those near sinusoids are primed for adipogenesis. Mechanical stimulation is crucial for the maintenance of the peri-arteriolar niche for osteogenesis and lymphopoiesis.