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.

粒细胞-单核细胞祖细胞（GMP）和单核-树突细胞祖细胞（MDP）在稳态过程中产生单核细胞，并响应感染期间需求的增加。认为这两个祖细胞均来自常见的髓祖细胞（CMP），并且推测层次关系（CMP-GMP-MDP-单核细胞）是单核细胞分化的基础。但是，在这里，我们证明了小鼠MDP源自CMP，而与GMP无关，并且GMP和MDP通过相似但截然不同的单核细胞定型祖细胞产生了单核细胞。GMP和MDP产生了经典（Ly6C ^hi）具有由其起源定义并影响其功能的基因表达特征的单核细胞。GMP产生了一个“中性粒细胞样”单核细胞的子集，而MDP产生了一个单核细胞的子集，该子集产生了单核细胞衍生的树突状细胞。在注射微生物成分后，还单独动员了GMP和MDP以产生髓样细胞类型的特定组合。因此，在稳态和感染后，GMP和MDP分化的平衡决定了髓样细胞的组成。