Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

摘要

Summary 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 (Ly6C hi ) 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. Graphical Abstract Display Omitted Highlights ? GMPs and MDPs independently produce functionally distinct inflammatory monocytes ? GMPs produce “neutrophil-like” inflammatory monocytes ? MDPs produce monocyte-derived dendritic cells (moDCs) ? Microbial stimuli differentially regulate monocyte production by GMPs and MDPs Yá?ez 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.