A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

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(1–6). LepR(+) cells are heterogeneous, including skeletal stem cells, osteogenic, and adipogenic progenitors(7–12), 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(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 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.