Evrard, MaximilienKwok, Immanuel W HChong, Shu ZhenTeng, Karen W WBecht, EtienneChen, JinmiaoSieow, Je LinPenny, Hweixian LeongChing, Goh ChiDevi, SapnaAdrover, Jose MLi, Jackson L YLiong, Ka HangTan, LeonardPoon, ZhiyongFoo, ShihuiChua, Jia WangSu, I-HsinBalabanian, KarlBachelerie, FrançoiseBiswas, Subhra KLarbi, AnisHwang, William Y KMadan, VikasKoeffler, H PhillipWong, Siew ChengNewell, Evan WHidalgo, AndresGinhoux, FlorentNg, Lai Guan2019-05-092019-05-092018-02Immunity. 2018; 48(2):364-37910747613http://hdl.handle.net/20.500.12105/7557Neutrophils 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.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/GranulopoiesisNeutrophil developmentNeutrophil ontogenyNeutrophil precursorsTraffickingAnimalsBone Marrow CellsCCAAT-Enhancer-Binding ProteinsCell LineageCell MovementCell ProliferationCells, CulturedGene Expression ProfilingHumansMiceNeoplasms, ExperimentalNeutrophilsAttribution-NonCommercial-NoDerivatives 4.0 Internacional29466759482364-379.e810.1016/j.immuni.2018.02.0021097-4180Immunityopen access