Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions
Authors:
- 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
Details:
Immunity, Volume 48, Issue 2, 2018-02-20
Article Link: Click here
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.