@article{18c2b1811aac4f428ec9c0f7e6b8b2bf,
title = "Identification of an Early Unipotent Neutrophil Progenitor with Pro-tumoral Activity in Mouse and Human Bone Marrow",
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.",
keywords = "CyTOF, T cell suppression, granulopoiesis, melanoma, neutrophil progenitor, sarcoma, scRNA-seq",
author = "Zhu, {Yanfang Peipei} and Lindsey Padgett and Dinh, {Huy Q.} and Paola Marcovecchio and Amy Blatchley and Runpei Wu and Erik Ehinger and Cheryl Kim and Zbigniew Mikulski and Gregory Seumois and Ariel Madrigal and Pandurangan Vijayanand and Hedrick, {Catherine C.}",
note = "Funding Information: We would like to thank K. Ley, G.D. Thomas, R. Hanna, Z.C. Fan, and J. Xie for helpful discussions; D. Yoakum for assistance with mouse colony management; the La Jolla Institute (LJI) Histology Core for assistance with cell morphology experiments; J. Day and the LJI Sequencing Core for assistance with RNA sequencing; and the LJI Flow Cytometry Core for assistance with FACS. The Mass Cytometry Core was supported by NIH grant 1S10OD018499-01 (to C.K. and S.C.). The melanoma patient study was supported by National Cancer Institute Cancer Center Support Grant P30 CA168524 and used the Biospecimen Shared Resource. This work was supported by NIH grants R01HL134236, P01HL136275, and R01CA202987 (all to C.C.H) and ADA7-12-MN-31 (04) (to C.C.H. and Y.P.Z). Funding Information: We would like to thank K. Ley, G.D. Thomas, R. Hanna, Z.C. Fan, and J. Xie for helpful discussions; D. Yoakum for assistance with mouse colony management; the La Jolla Institute (LJI) Histology Core for assistance with cell morphology experiments; J. Day and the LJI Sequencing Core for assistance with RNA sequencing; and the LJI Flow Cytometry Core for assistance with FACS. The Mass Cytometry Core was supported by NIH grant 1S10OD018499-01 (to C.K. and S.C.). The melanoma patient study was supported by National Cancer Institute Cancer Center Support Grant P30 CA168524 and used the Biospecimen Shared Resource. This work was supported by NIH grants R01HL134236 , P01HL136275 , and R01CA202987 (all to C.C.H) and ADA7-12-MN-31 (04) (to C.C.H. and Y.P.Z). Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = aug,
day = "28",
doi = "10.1016/j.celrep.2018.07.097",
language = "English (US)",
volume = "24",
pages = "2329--2341.e8",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}
