作者
Maximilien Evrard,Immanuel Kwok,Shu Zhen Chong,Karen Wei Weng Teng,Étienne Becht,Jinmiao Chen,Je Lin Sieow,Hweixian Leong Penny,Goh Chi Ching,Sapna Devi,José M. Adrover,J Li,Ka Hang Liong,Leonard Tan,Zhiyong Poon,Shihui Foo,Jia Wang Chua,I-hsin Su,Karl Balabanian,Françoise Bachelerie,Subhra K. Biswas,Anis Larbi,William Hwang,Vikas Madan,H. Phillip Koeffler,Siew Cheng Wong,Evan W. Newell,Andrés Hidalgo,Florent Ginhoux,Lai Guan Ng
摘要
Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half-life. Although it is established that neutrophils are derived from the granulocyte-macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell-cycle-based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non-proliferating immature neutrophils and mature neutrophils. Transcriptomic profiling and functional analysis revealed that preNeu require the C/EBPε transcription factor for their generation from the GMP, and their proliferative program is substituted by a gain of migratory and effector function as they mature. preNeus expand under microbial and tumoral stress, and immature neutrophils are recruited to the periphery of tumor-bearing mice. In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses.