Distinct CSF1 Micro-Environments Maintain Monocytes within a Perivascular Bone Marrow Niche
42 Pages Posted: 26 May 2020 Sneak Peek Status: Under ReviewMore...
The bone marrow niche factors that sustain monocytes – phagocytes with complex functions in the circulation and peripheral tissues – and the functionally important cells that produce them, are poorly defined. Here, we conditionally deleted macrophage colony stimulating factor 1 (Csf1) in adult mice and show that CSF1 regulated differentiation and survival of monocytes and their precursor cells independent of its effects on bone development. Specifically, CSF1 produced by sinusoidal endothelial cells (ECs) but not leukocytes or stromal cells selectively maintained abundance of nonclassical Ly6Cnegative monocytes. Ly6Chigh monocytes, on the other hand, required CSF1 produced by ECs as well as leptin receptor (Lepr)-expressing perivascular stromal cells. Importantly, osteoblast-derived CSF1 critically supported bone formation and hematopoiesis during early development but did not contribute to maintenance of monocytes in adulthood. Our findings reveal classical and non-classical monocytes receive support by distinct cellular sources of CSF1 within a perivascular bone marrow niche.
Keywords: bone marrow niche, monocyte, CSF1, endothelial cell, perivascular stromal cell
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