Nature Cell Biology ( IF 21.3 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41556-019-0437-8 Yasuhito Yahara 1, 2 , Tomasa Barrientos 1 , Yuning J Tang 1, 3 , Vijitha Puviindran 1 , Puviindran Nadesan 1 , Hongyuan Zhang 1, 4 , Jason R Gibson 5 , Simon G Gregory 5 , Yarui Diao 1, 4 , Yu Xiang 4 , Yawar J Qadri 6 , Tomokazu Souma 7 , Mari L Shinohara 8, 9 , Benjamin A Alman 1
Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies—labelling cells expressing Cx3cr1, Csf1r or Flt3—to identify the precursors of osteoclasts in mice. We identified an erythromyeloid progenitor (EMP)-derived osteoclast precursor population. Yolk-sac macrophages of EMP origin produced neonatal osteoclasts that can create a space for postnatal bone marrow haematopoiesis. Furthermore, EMPs gave rise to long-lasting osteoclast precursors that contributed to postnatal bone remodelling in both physiological and pathological settings. Our single-cell RNA-sequencing data showed that EMP-derived osteoclast precursors arose independently of the haematopoietic stem cell (HSC) lineage and the data from fate tracking of EMP and HSC lineages indicated the possibility of cell–cell fusion between these two lineages. Cx3cr1+ yolk-sac macrophage descendants resided in the adult spleen, and parabiosis experiments showed that these cells migrated through the bloodstream to the remodelled bone after injury.
中文翻译:
红细胞骨髓祖细胞产生大量破骨细胞,有助于骨稳态和修复
破骨细胞是降解骨的单核细胞/巨噬细胞谱系的多核细胞。在这里,我们使用谱系追踪研究——标记表达Cx3cr1、Csf1r或Flt3的细胞——鉴定小鼠破骨细胞的前体。我们确定了一个红细胞祖细胞 (EMP) 衍生的破骨细胞前体群。EMP 起源的卵黄囊巨噬细胞产生了新生儿破骨细胞,可以为出生后的骨髓造血创造空间。此外,EMPs 产生了持久的破骨细胞前体,在生理和病理环境中都有助于产后骨重塑。我们的单细胞 RNA 测序数据显示 EMP 衍生的破骨细胞前体独立于造血干细胞 (HSC) 谱系产生,来自 EMP 和 HSC 谱系的命运追踪数据表明这两个谱系之间存在细胞-细胞融合的可能性。CX3CR1 + 卵黄囊巨噬细胞后代存在于成人脾脏中,联体共生实验表明,这些细胞在损伤后通过血流迁移到重塑的骨骼中。