1. Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions
- Author
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José M. Adrover, Subhra K. Biswas, Shu Zhen Chong, Jackson LiangYao Li, Anis Larbi, Zhiyong Poon, Etienne Becht, Shihui Foo, Goh Chi Ching, Ka Hang Liong, Hweixian Leong Penny, Florent Ginhoux, Maximilien Evrard, Je Lin Sieow, Karl Balabanian, Jia Wang Chua, Françoise Bachelerie, Vikas Madan, Andrés Hidalgo, I-hsin Su, William Hwang, Lai Guan Ng, Immanuel Kwok, Siew Cheng Wong, Karen Wei Weng Teng, Sapna Devi, Leonard Tan, Jinmiao Chen, H. Phillip Koeffler, Evan W. Newell, and School of Biological Sciences
- Subjects
0301 basic medicine ,Granulopoiesis ,Neutrophils ,Immunology ,Inflammation ,Bone Marrow Cells ,Biology ,Transcriptome ,03 medical and health sciences ,Mice ,0302 clinical medicine ,trafficking ,Cell Movement ,medicine ,Immunology and Allergy ,Animals ,Humans ,Mass cytometry ,Cell Lineage ,Cells, Cultured ,Progenitor ,Cell Proliferation ,Ccaat-enhancer-binding proteins ,Effector ,Gene Expression Profiling ,Biological sciences [Science] ,Neoplasms, Experimental ,neutrophil ontogeny ,Cell biology ,neutrophil precursors ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,CCAAT-Enhancer-Binding Proteins ,Bone marrow ,medicine.symptom ,neutrophil development - 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. We thank all members of L.G.N laboratory, the SIgN (Singapore Immunology Network) flow-cytometry team, the SIgN functional genomics team for their assistance with transcriptomics, and the SIgN mouse core facility for their technical help and support. This research was funded by SIgN core funding, A*STAR (Agency for Science, Technology and Research), Singapore. Sí
- Published
- 2017