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Preparation of Whole Bone Marrow for Mass Cytometry Analysis of Neutrophil-lineage Cells
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Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and

Maximilien Evrard1, Immanuel W H Kwok2, Shu Zhen Chong1

  • 1Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, 138648 Singapore.

Immunity
|February 22, 2018
PubMed

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:
Granulopoiesisneutrophil developmentneutrophil ontogenyneutrophil precursorstrafficking

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