Identification of an Early Unipotent Neutrophil Progenitor with Pro-tumoral Activity in Mouse and Human Bone Marrow

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

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

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 languageEnglish (US)
Pages (from-to)2329-2341.e8
JournalCell Reports
Volume24
Issue number9
DOIs
StatePublished - Aug 28 2018
Externally publishedYes

Keywords

  • CyTOF
  • T cell suppression
  • granulopoiesis
  • melanoma
  • neutrophil progenitor
  • sarcoma
  • scRNA-seq

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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