A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

Abstract

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.

One Sentence Summary:

A peri-arteriolar niche in the bone marrow for osteogenesis and lymphopoiesis is maintained by mechanical stimulation and is depleted during aging.