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

Abstract

The osteoclast is a multinucleated monocyte/macrophage lineage cell that degrades bone. Here we used lineage tracing studies, labeling cells expressing Cx3cr1, Csf1r, or Flt3 to identify the precursors of osteoclast 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 hematopoiesis. Furthermore, EMPs gave rise to long-lasting osteoclast precursors that contributed to postnatal bone remodeling in both physiological and pathological settings. Our single cell RNA-sequencing data showed that EMP-derived osteoclast precursors arose independently from hematopoietic stem cell (HSC) lineage and the data from fate tracking of EMP-and HSC-lineage provided a possibility of cell-Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Yolk-sac-derived macrophages progressively expand in the mouse kidney with age

“…While further investigation is required, these results suggest that the tdTomato-positive circulating progenitors may have a significant proliferative capacity and can slowly contribute to the adult renal macrophage pool. Currently, the origin of the circulating CX3CR1-lineage cells is not known but we speculate that one site is the spleen, which we recently identified as a reservoir of CX3CR1 + yolk-sac macrophages [28].…”

“…This efficiently and irreversibly labels yolk-sac-derived macrophages with the tdTomato reporter. Importantly, the approach does not label fetal monocytes or HSCs [5,28].…”

“…To further delineate the chronological shift of renal macrophages, we examined the HSC contribution to renal macrophages using the Flt3-Cre; Rosa26 tdTomato mouse line [1, 28,30]. This mouse line irreversibly labels fetal and adult HSC-derived multipotent hematopoietic progenitors and their progeny with tdTomato expression.…”

“…Parabiosis surgery. Parabiosis surgery was performed as previously described [28]. Briefly, a longitudinal skin incision was performed from elbow to knee joint to each mouse.…”

Bone marrow adipogenic lineage precursors (MALPs) promote osteoclastogenesis in bone remodeling and pathologic bone loss

“…Therefore, the pseudotime trajectory analysis might not be inclusive. Moreover, recent studies have demonstrated that tissue-resident macrophages contain both embryonic stage-derived macrophages and adult HSC-derived macrophages (44) and that osteoclasts in adult bone are also fusion of cells originated from these two types of macrophages (45,46), raising a concern whether scRNA-seq analysis could distinguish these two sources of progenitors. Nevertheless, our analysis revealed that Mϕα cells differentiate into two types of terminal cells, osteoclasts that eat bone matrix and Mϕβ that eat apoptotic cells in bone.…”