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. 2018 Feb 20;48(2):364-379.e8.
doi: 10.1016/j.immuni.2018.02.002.

Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions

Maximilien Evrard  1 , Immanuel W H Kwok  2 , Shu Zhen Chong  3 , Karen W W Teng  3 , Etienne Becht  3 , Jinmiao Chen  3 , Je Lin Sieow  3 , Hweixian Leong Penny  3 , Goh Chi Ching  3 , Sapna Devi  3 , José Maria Adrover  4 , Jackson L Y Li  5 , Ka Hang Liong  3 , Leonard Tan  3 , Zhiyong Poon  6 , Shihui Foo  3 , Jia Wang Chua  3 , I-Hsin Su  7 , Karl Balabanian  8 , Françoise Bachelerie  8 , Subhra K Biswas  3 , Anis Larbi  3 , William Y K Hwang  6 , Vikas Madan  9 , H Phillip Koeffler  10 , Siew Cheng Wong  3 , Evan W Newell  3 , Andrés Hidalgo  11 , Florent Ginhoux  3 , Lai Guan Ng  12
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Free article

Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions

Maximilien Evrard et al. Immunity. .
Free article

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/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.

Keywords: Granulopoiesis; neutrophil development; neutrophil ontogeny; neutrophil precursors; trafficking.

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