Abstract
Neutrophils are short-lived cells that play important roles in both health and disease. Neutrophils and monocytes originate from the granulocyte monocyte progenitor (GMP) in bone marrow; however, unipotent neutrophil progenitors are not well defined. Here, we use cytometry by time of flight (CyTOF) and single-cell RNA sequencing (scRNA-seq) methodologies to identify a committed unipotent early-stage neutrophil progenitor (NeP) in adult mouse bone marrow. Importantly, we found a similar unipotent NeP (hNeP) in human bone marrow. Both NeP and hNeP generate only neutrophils. NeP and hNeP both significantly increase tumor growth when transferred into murine cancer models, including a humanized mouse model. hNeP are present in the blood of treatment-naive melanoma patients but not of healthy subjects. hNeP can be readily identified by flow cytometry and could be used as a biomarker for early cancer discovery. Understanding the biology of hNeP should allow the development of new therapeutic targets for neutrophil-related diseases, including cancer. Zhu et al. discover an early unipotent neutrophil progenitor (NeP) in mouse and human bone marrow using high-dimensional profiling. NeP expand in cancer, suppress T cells, and promote tumor growth in vivo. NeP is found in the blood of human melanoma patients, suggesting that NeP could be a new cancer biomarker.
Original language | English (US) |
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Pages (from-to) | 2329-2341.e8 |
Journal | Cell Reports |
Volume | 24 |
Issue number | 9 |
DOIs | |
State | Published - Aug 28 2018 |
Externally published | Yes |
Keywords
- CyTOF
- T cell suppression
- granulopoiesis
- melanoma
- neutrophil progenitor
- sarcoma
- scRNA-seq
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology