Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes. Although studies have proposed lineage heterogeneity within GMPs, it is unclear if committed progenitors already exist among these progenitors and how they may behave differently during inflammation. By combining single-cell transcriptomic and proteomic analyses, we identified the early committed progenitor within the GMPs responsible for the strict production of neutrophils, which we designate as proNeu1. Our dissection of the GMP hierarchy led us to further identify a previously unknown intermediate proNeu2 population. Similar populations could be detected in human samples. proNeu1s, but not proNeu2s, selectively expanded during the early phase of sepsis at the expense of monocytes. Collectively, our findings help shape the neutrophil maturation trajectory roadmap and challenge the current definition of GMPs.

粒细胞-单核细胞祖细胞（GMP）先前已被定义为具有产生各种髓系子代细胞（如嗜中性粒细胞和单核细胞）的潜力。尽管研究已经提出了GMP内的谱系异质性，但尚不清楚这些祖细胞中是否已经存在定型祖细胞，以及它们在炎症过程中的行为如何不同。通过结合单细胞转录组学和蛋白质组学分析，我们在GMP中确定了负责严格生产嗜中性粒细胞的早期承诺祖细胞，我们将其指定为proNeu1。我们对GMP层次结构的剖析导致我们进一步确定了以前未知的中间proNeu2群体。在人类样本中可以检测到相似的种群。proNeu1s，而不是proNeu2s，在败血症的早期选择性扩张，但以单核细胞为代价。