Details

Autor(en) / Beteiligte

• 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, José Maria
• 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
• Ginhoux, Florent
• Ng, Lai Guan

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2018-02, Vol.48 (2), p.364-379.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Proliferation activity identifies committed neutrophil precursor in mice and humans•Neutrophil subsets possess distinct transcriptomic and functional signatures•Defect in neutrophil development leads to impaired neutrophil-mediated responses•Increased circulating immature neutrophils are associated with cancer progression The neutrophil differentiation pathway is poorly defined. Evrard et. al. demonstrate a workflow of characterizing bone marrow neutrophil subsets on the basis of their proliferative capacity and molecular signatures and thereby define the developmental trajectory and functional properties of neutrophils.