Yáñez Alberto, Coetzee Simon G, Olsson Andre, Muench David E, Berman Benjamin P, Hazelett Dennis J, Salomonis Nathan, Grimes H Leighton, Goodridge Helen S
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; The Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Immunity. 2017 Nov 21;47(5):890-902.e4. doi: 10.1016/j.immuni.2017.10.021.
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) 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（GMPs）和单核细胞-树突状细胞祖细胞（MDPs）在稳态期间以及感染期间需求增加时产生单核细胞。这两种祖细胞群体都被认为起源于共同髓系祖细胞（CMPs），并且推测单核细胞分化的基础是一种层级关系（CMP-GMP-MDP-单核细胞）。然而，在此我们证明，小鼠MDPs独立于GMPs起源于CMPs，并且GMPs和MDPs通过相似但不同的单核细胞定向祖细胞产生单核细胞。GMPs和MDPs产生具有由其起源所定义并影响其功能的基因表达特征的经典（Ly6C）单核细胞。GMPs产生了一部分“中性粒细胞样”单核细胞，而MDPs产生了一部分可分化为单核细胞来源树突状细胞的单核细胞。在注射微生物成分后，GMPs和MDPs也被独立动员以产生特定组合的髓系细胞类型。因此，在稳态期间以及感染后，GMP和MDP分化的平衡塑造了髓系细胞库。
