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Immunity. 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.

Author information

1
Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, 138648 Singapore. Electronic address: maximilien.evrard@unimelb.edu.au.
2
Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, 138648 Singapore; School of Biological Sciences, Nanyang Technological University, 637551 Singapore.
3
Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, 138648 Singapore.
4
Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
5
Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, 138648 Singapore; Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
6
Department of Hematology, Singapore General Hospital, 169856 Singapore.
7
School of Biological Sciences, Nanyang Technological University, 637551 Singapore.
8
Inflammation Chemokines and Immunopathology, INSERM, UMR 996, Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 92140 Clamart, France.
9
Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore.
10
Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore; Cedars-Sinai Medical Center, Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA, USA; Department of Hematology-Oncology, National University Cancer Institute of Singapore, National University Hospital, 119074 Singapore.
11
Area of Cell and Developmental Biology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain; Institute for Cardiovascular Prevention, LMU, Munich 80336, Germany.
12
Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, 138648 Singapore; School of Biological Sciences, Nanyang Technological University, 637551 Singapore. Electronic address: ng_lai_guan@immunol.a-star.edu.sg.

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

PMID:
29466759
DOI:
10.1016/j.immuni.2018.02.002
[Indexed for MEDLINE]
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