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.

Overall design

Neutrophil progenitor isolated from mouse and human fresh bone marrow without treatment were sequeced to explore heterogeneities; 3' Transcriptome sequencing (10X genomics)

Contributors

Yanfang Peipei Zhu 1, Lindsey Padgett 2, Huy Q Dinh 2, Paola Marcovecchio 2, Amy Blatchley 2, Runpei Wu 2, Erik Ehinger 2, Cheryl Kim 3, Zbigniew Mikulski 2, Gregory Seumois 4, Ariel Madrigal 4, Pandurangan Vijayanand 4, Catherine C Hedrick 5

Contact

hedrick@lji.org.(Catherine C Hedrick)