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

55 Pages Posted: 6 Jun 2018 Publication Status: Published

See all articles by Yanfang Peipei

Yanfang Peipei

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Paola Marcovecchio

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Amy Blatchley

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Lindsey Padgett

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Runpei Wu

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Erik Ehinger

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Cheryl Kim

La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility

Zbigniew Mikulski

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Gregory Seumois

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Ariel Madrigal

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Huy Dinh

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

Pandurangan Vijayanand

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Catherine C. Hedrick

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

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Abstract

Neutrophils are short-lived immune cells that play important roles in a variety of diseases. The oligopotent Granulocyte Monocyte Progenitors (GMP) in the bone marrow give rise to monocytes and all granulocytes. Although several monocyte progenitors have been identified in mouse bone marrow, the unipotent neutrophil progenitors are still 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 in adult mouse bone marrow. Importantly, we also discovered a similar unipotent, committed neutrophil progenitor (hNeP) that is present in healthy human bone marrow. Both mouse and human progenitors demonstrate unipotent neutrophil potency in vivo. Study of the identified mouse (NeP) and human (hNeP) neutrophil progenitors in cancer revealed that both NeP and hNeP significantly increased tumor growth when transferred into murine cancer models, including a humanized model. Further, we discovered that the hNeP was present in the blood of human patients recently diagnosed with melanoma, and could be readily identified by flow cytometry, suggesting that this human neutrophil progenitor could be used as a biomarker for early cancer discovery. The discovery of this early committed unipotent neutrophil progenitor in humans will allow for development of important new therapeutic targets for regulation of neutrophil levels and function in disease.

Suggested Citation

Peipei, Yanfang and Marcovecchio, Paola and Blatchley, Amy and Padgett, Lindsey and Wu, Runpei and Ehinger, Erik and Kim, Cheryl and Mikulski, Zbigniew and Seumois, Gregory and Madrigal, Ariel and Dinh, Huy and Vijayanand, Pandurangan and Hedrick, Catherine C., Identification of an Early Unipotent Neutrophil Progenitor with Pro-Tumoral Activity in Mouse and Human Bone Marrow (2018). Available at SSRN: https://ssrn.com/abstract=3188497 or http://dx.doi.org/10.2139/ssrn.3188497
This version of the paper has not been formally peer reviewed.

Yanfang Peipei (Contact Author)

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology ( email )

La Jolla, CA 92037
United States

Paola Marcovecchio

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Amy Blatchley

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Lindsey Padgett

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Runpei Wu

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Erik Ehinger

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Cheryl Kim

La Jolla Institute for Allergy and Immunology (LIAI) - Flow Cytometry Core Facility

La Jolla, CA 92037
United States

Zbigniew Mikulski

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Gregory Seumois

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

La Jolla, CA 92037
United States

Ariel Madrigal

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

La Jolla, CA 92037
United States

Huy Dinh

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology

La Jolla, CA 92037
United States

Pandurangan Vijayanand

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

La Jolla, CA 92037
United States

Catherine C. Hedrick

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Inflammation Biology ( email )

La Jolla, CA 92037
United States

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