Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair

Nat Cell Biol. 2020 Jan;22(1):49-59. doi: 10.1038/s41556-019-0437-8. Epub 2020 Jan 6.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / metabolism
  • Homeostasis / physiology*
  • Macrophages / metabolism
  • Mice
  • Osteoclasts / metabolism*
  • Yolk Sac / metabolism*