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Evrard, Maximilien; Kwok, Immanuel W. H.; Chong, Shu Zhen; Teng, Karen W. W.; Becht, Etienne; Chen, Jinmiao; Sieow, Je Lin; Penny, Hweixian Leong; Ching, Goh Chi; Devi, Sapna; Adrover, Jose Maria; Li, Jackson L. Y.; Liong, Ka Hang; Tan, Leonard; Poon, Zhiyong; Foo, Shihui; Chua, Jia Wang; Su, I-Hsin; Balabanian, Karl; Bachelerie, Francois; Biswas, Subhra K.; Larbi, Anis; Hwang, William Y. K.; Madan, Vikas; Koeffler, H. Phillip; Wong, Siew Cheng; Newell, Evan W.; Hidalgo, Andres; Ginhoux, Florent; Ng, Lai Guan (2018): Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions. In: Immunity, Vol. 48, No. 2: pp. 364-379
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Abstract

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/EBP epsilon 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.