Identification of a Human Clonogenic Progenitor with Strict Monocyte Differentiation Potential: A Counterpart of Mouse cMoPs

Kawamura, Shunsuke; Onai, Nobuyuki; Miya, Fuyuki; Sato, Taku; Tsunoda, Tatsuhiko; Kurabayashi, Kazutaka; Yotsumoto, Satoshi; Kuroda, Seika; Takenaka, Katsuto; Akashi, Koichi; Ohteki, Toshiaki

doi:10.1016/j.immuni.2017.04.019

Cited by 80 publications

(86 citation statements)

References 50 publications

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“…Two different control groups were used in this experiment: one control group received only PBS for adoptive transfer, the other group received human cMoP as a source of human monocyte progenitors. Human cMoP were sorted from the same human BM donor using the panel described previously (Kawamura et al, 2017). One day one after adoptive transfer of progenitors, 1 × 106 human osteosarcoma cells were injected SubQ to the rear flank of mice in all 4 recipient groups.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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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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Section: Resultsmentioning

confidence: 99%

“…Comparable to GMP, myeloblasts are known to have both granulocytic and monocytic potentials (Borregaard, 2010). The use of CD64 identified a human CD34 + CD64 hi monocyte progenitor within human GMPs (Kawamura et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…A recent paper describing human monocyte-committed progenitors cast doubt on the presumed hierarchical relationship between human GMPs and MDPs, because GMPs failed to produce DCs in in vitro assays (Kawamura et al, 2017). Thus the two separate pathways of monocyte production by GMPs and MDPs that we have demonstrated in mice likely also exist in humans.…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

et al. 2017

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Summary Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.

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“…Monocytes circulate in peripheral blood during steady state after developing from a lineage‐committed bone marrow progenitor, the common monocyte progenitor (cMoP), which was first discovered in mouse . The human cMoP was recently identified in human umbilical cord blood and bone marrow . In both mouse and human, cMoPs are unipotent monocyte progenitors that express the stem cell marker CD117, as well as the C‐type lectin CLEC12A and CD64.…”

Section: Monocyte Developmental Origins and Fatesmentioning

confidence: 99%

“…GMPs are a heterogeneous population that contains multiple progenitors with various degrees of restriction for differentiation into monocyte, DC, and granulocyte lineages . Refining the definition of conventional human GMPs to include only CLEC12A hi CD64 int cells excludes cells with lymphoid or DC potential and identifies a population of cells that sequentially produces cMoPs and monocytes . However, traditionally defined MDPs (CD115 + CD116–) phenotypically overlap with both GMPs and cMoPs, indicating that current definitions of progenitor populations are likely heterogeneous.…”

Section: Monocyte Developmental Origins and Fatesmentioning

confidence: 99%

Monocyte heterogeneity and functions in cancer

Olingy

Dinh

Hedrick

2019

Journal of Leukocyte Biology

388

310

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Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding of monocytes has advanced from viewing these cells as a homogenous population to a heterogeneous system of cells that display diverse responses to different stimuli. During cancer, different monocyte subsets perform functions that contribute to both pro‐ and antitumoral immunity, including phagocytosis, secretion of tumoricidal mediators, promotion of angiogenesis, remodeling of the extracellular matrix, recruitment of lymphocytes, and differentiation into tumor‐associated macrophages and dendritic cells. The ability of cancer to evade immune recognition and clearance requires protumoral signals to outweigh ongoing attempts by the host immune system to prevent tumor growth. This review discusses current understanding of monocyte heterogeneity during homeostasis, highlights monocyte functions in cancer progression, and describes monocyte‐targeted therapeutic strategies for cancer treatment.

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Identification of a Human Clonogenic Progenitor with Strict Monocyte Differentiation Potential: A Counterpart of Mouse cMoPs

Cited by 80 publications

References 50 publications

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

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

Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

Monocyte heterogeneity and functions in cancer

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