Neutrophils are the most abundant peripheral immune cells and thus, are continually replenished by bone marrow-derived progenitors. Still, how newly identified neutrophil subsets fit into the bone marrow neutrophil lineage remains unclear. Here, we use mass cytometry to show that two recently defined human neutrophil progenitor populations contain a homogeneous progenitor subset we term “early neutrophil progenitors” (eNePs) (Lin⁻CD66b⁺CD117⁺CD71⁺). Surface marker- and RNA-expression analyses, together with in vitro colony formation and in vivo adoptive humanized mouse transfers, indicate that eNePs are the earliest human neutrophil progenitors. Furthermore, we identified CD71 as a marker associated with the earliest neutrophil developmental stages. Expression of CD71 marks proliferating neutrophils, which were expanded in the blood of melanoma patients and detectable in blood and tumors from lung cancer patients. In summary, we establish CD117⁺CD71⁺ eNeP as the inceptive human neutrophil progenitor and propose a refined model of the neutrophil developmental lineage in bone marrow.

中性粒细胞是最丰富的外周免疫细胞，因此由骨髓来源的祖细胞不断补充。尽管如此，新发现的中性粒细胞亚群如何融入骨髓中性粒细胞谱系仍不清楚。在这里，我们使用质谱流式细胞术来显示两个最近定义的人类中性粒细胞祖细胞群包含一个同质祖细胞亚群，我们称之为“早期中性粒细胞祖细胞”（eNePs）（Lin ⁻ CD66b ⁺ CD117 ⁺ CD71 ⁺）。表面标记和 RNA 表达分析，以及体外集落形成和体内过继人源化小鼠转移表明，eNePs 是最早的人类中性粒细胞祖细胞。此外，我们将 CD71 鉴定为与最早的中性粒细胞发育阶段相关的标志物。CD71 的表达标志着中性粒细胞的增殖，这些中性粒细胞在黑色素瘤患者的血液中扩增，并可在肺癌患者的血液和肿瘤中检测到。总之，我们建立 CD117 ⁺ CD71 ⁺ eNeP 作为初始人类中性粒细胞祖细胞，并提出了骨髓中性粒细胞发育谱系的精细模型。