Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7557
Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions
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 M CNIC | Li, Jackson L Y | Liong, Ka Hang | Tan, Leonard | Poon, Zhiyong | Foo, Shihui | Chua, Jia Wang | Su, I-Hsin | Balabanian, Karl | Bachelerie, Françoise | Biswas, Subhra K | Larbi, Anis | Hwang, William Y K | Madan, Vikas | Koeffler, H Phillip | Wong, Siew Cheng | Newell, Evan W | Hidalgo, Andrés CNIC | Ginhoux, Florent | Ng, Lai Guan
Immunity. 2018; 48(2):364-379
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.
Animals | Bone Marrow Cells | CCAAT-Enhancer-Binding Proteins | Cell Lineage | Cell Movement | Cell Proliferation | Cells, Cultured | Gene Expression Profiling | Humans | Mice | Neoplasms, Experimental | Neutrophils
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