Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar but distinct monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Yáñez et al. show that functionally distinct inflammatory monocytes, including those producing monocyte-derived DCs and a “neutrophil-like” subset, arise from bone marrow progenitors via two independent pathways. Their analyses reveal that the repertoire of myeloid cells produced under steady-state and stress conditions depends on which progenitors are mobilized to differentiate.
Bibliographical noteFunding Information:
This study was supported by funds from the Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center (to H.S.G.), development funds from Cedars-Sinai Medical Center (to S.C., D.H., and B.B.), a grant from the National Institutes of Health ( R01HL122661 to H.L.G.), a Careers in Immunology fellowship from the American Association of Immunologists (to A.Y. and H.S.G.), and a Scholar Award from the American Society of Hematology (to A.Y.). We thank Dr. Ritchie Ho for helpful discussions.
© 2017 Elsevier Inc.
- dendritic cell
- granulocyte-monocyte progenitor
- monocyte progenitor
- monocyte-dendritic cell progenitor
- myeloid cell
- myeloid progenitor