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Zhu, Yanfang Peipei; Padgett, Lindsey; Dinh, Huy Q.; Marcovecchio, Paola; Blatchley, Amy; Wu, Runpei; Ehinger, Erik; Kim, Cheryl; Mikulski, Zbigniew; Seumois, Gregory; Madrigal, Ariel; Vijayanand, Pandurangan; Hedrick, Catherine C.
Cell reports (Cambridge), 08/2018, Volume: 24, Issue: 9Journal Article
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. Display omitted •High-dimensional analysis of human bone marrow reveals neutrophil progenitor (NeP)•NeP is unipotent and produces only neutrophils in vivo•NeP suppresses T cell activation and promotes tumor growth in mouse models in vivo•NeP expands in blood of humans with melanoma and in tumor-bearing mice 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.
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