[PDF][PDF] Identification of an early unipotent neutrophil progenitor with pro-tumoral activity in mouse and human bone marrow

YP Zhu, L Padgett, HQ Dinh, P Marcovecchio… - Cell reports, 2018 - cell.com
YP Zhu, L Padgett, HQ Dinh, P Marcovecchio, A Blatchley, R Wu, E Ehinger, C Kim…
Cell reports, 2018cell.com
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 …
Summary
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.
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