Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1^op/op) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood. However, ubiquitous deletion of Csf1 conditionally in adulthood decreased monocyte survival, differentiation, and migration, independent of its effects on bone development. Bone histology revealed that monocytes reside near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing perivascular mesenchymal stromal cells (MSCs). Targeted deletion of Csf1 from sinusoidal ECs selectively reduced Ly6C⁻ monocytes, whereas combined depletion of Csf1 from ECs and MSCs further decreased Ly6C^hi cells. Moreover, EC-derived CSF-1 facilitated recovery of Ly6C⁻ monocytes and protected mice from weight loss following induction of polymicrobial sepsis. Thus, monocytes are supported by distinct cellular sources of CSF-1 within a perivascular BM niche.

巨噬细胞集落刺激因子 1 (CSF-1) 在维持髓系细胞中起关键作用。然而，先天性全身性脑脊液 1 缺乏症 ( Csf1 ^op/op ) 会导致严重的肌肉骨骼缺陷，从而可能间接影响造血功能。事实上，我们在这里表明，骨谱系衍生的Csf1 可以防止发育异常，但对成年期的垄断没有影响。然而，在成年期普遍存在的Csf1有条件缺失会降低单核细胞的存活、分化和迁移，与其对骨骼发育的影响无关。骨组织学显示单核细胞位于血窦内皮细胞 (EC) 和瘦素受体 ( Lepr)-表达血管周围间充质基质细胞 (MSCs)。从正弦 ECs中靶向删除Csf1选择性地减少 Ly6C ^-单核细胞，而从 ECs 和 MSCs 中联合消耗Csf1进一步减少 Ly6C ^hi细胞。此外，EC 衍生的 CSF-1 促进了 Ly6C ^-单核细胞的恢复，并保护小鼠在诱导多种微生物败血症后体重减轻。因此，单核细胞由血管周围 BM 生态位内不同细胞来源的 CSF-1 支持。