Identification of an Early Unipotent Neutrophil Progenitor with Pro-Tumoral Activity in Mouse and Human Bone Marrow
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PROVIDER: PRJNA481247 | ENA |
REPOSITORIES: ENA
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Project description: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, particularly in cancers, where neutrophils play a significant role.
2018-08-28 | GSE117131 | GEO
Project description:Discovery of a Pro-Tumoral Clonogenic Unipotent Neutrophil Progenitor in Mouse and Human Bone Marrow
| PRJNA481252 | ENA
Project description: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, particularly in cancers, where neutrophils play a significant role.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, particularly in cancers, where neutrophils play a significant role.
2018-07-17 | GSE117129 | GEO
Project description: Not available
| S-EPMC6542273 | biostudies-literature
Project description:Identification of a CD117+ CD71+ early unipotent neutrophil progenitor population in human bone marrow
| PRJNA641887 | ENA
Project description:Neutrophils play critical roles in health and disease. Due to their very short half-life in blood and tissue, neutrophils are constantly replenished by bone marrow progenitors. Thus, a comprehensive understanding of bone marrow neutrophil development is of paramount importance to identify how neutrophil production is altered in disease. Recently, two novel human neutrophil progenitor populations were identified; ‘human neutrophil progenitor’ or ‘hNeP’ (Lin- CD66b+ CD117+ ) and ‘neutrophil precursor’ or ‘preNeu’ (Lin- CD66b+ CD15+ CD49d+ ). How these subsets fit into the neutrophil lineage is unclear. By using mass and flow cytometry, we show that hNeP are a heterogenous population containing a homogeneous progenitor subset termed ‘early neutrophil progenitor’ or ‘eNeP’ (Lin- CD66b+ CD117+ CD71+ ). Surface marker and RNA expression, together with the ability to form colonies in vitro and exclusively produce neutrophils in vivo in humanized NSG-SGM3 mouse transfer experiments indicate that eNeP are hierarchically the ‘earliest’ cells within preNeu. eNeP constitute ~0.14% of human bone marrow neutrophils, while preNeu constitute ~5% of bone marrow neutrophils. Furthermore, we have identified CD71 as a novel neutrophil surface marker associated with distinct early neutrophil developmental stages. Intriguingly, CD71+ characterizes proliferating neutrophils, which are expanded in the blood of melanoma and lung cancer patients and detectable in human lung tumors. Collectively, our findings i) identify CD117+ CD71+ eNeP as an early neutrophil progenitor population, ii) introduce a unified model of human neutrophil bone marrow development, iii) identify novel surface markers for distinct neutrophil developmental stages and iv) provide evidence for neutrophil progenitor expansion in cancer.
2020-08-04 | GSE153263 | GEO
Project description:Purpose: Investigate the gene accessibility change of neutrophils from PGE2 stimulation and identify the posibility for PGE2 could induce lung neutrophil like characteristics. Methods: Isolated bone marrow neutrophils with Percoll gradient are treated with 10 μM of PGE2 for 24 hours. Conclusion: Chromatin accessibility for the genes that were upregulated in lung neutrophils and PGE2 treated neutrophils were increased, so PGE2 could induce lung neutrophil like characteristics with change chromatin accessibility.
2022-08-01 | GSE199772 | GEO
Project description:The purpose of this study is to learn the dynamic transcriptomic and molecular changes during neutrophil development. We investigated the gene expression profiles of purified morphology-defined neutrophil populations. Promyelocytes (PMs), myelocytes (MCs), metamyelocytes (MMs), band neutrophils and segmented neutrophils (BN/SNs) were isolated by FACS based on differential expression of C-Kit and Ly6g.Their identities were confirmed by morphological examination. Bulk RNA sequencing was then performed to reveal the gene expression profiles and molecular signatures of each cell population. Detailed analysis of gene expression revealed that MBs highly expressed the stem cell marker Cd34 and translation-related genes such as Eef1a1, while the highest expression of primary granule-related genes such as Mpo, Elane, Prtn3, and Cstg was detected in the PM population. MCs and MMs were highly proliferative neutrophils expressing high levels of cell cycle-related genes which were significantly downregulated in mature neutrophils. Finally, this study provides a framework for the detail study of the neutrophil development and for the future application in the modulation of the granulopoiesis under pathological conditions.
2020-05-27 | GSE137538 | GEO
Project description:Characterisation of the extracellular vesicles shed by follicular lymphoma B cells that induce the polarization of bone marrow stroma cell toward a pro-tumoral niche.
2021-02-08 | PXD023749 | Pride
Project description:RNAseq was performed on bone marrow GMP and neutrophil subsets to understand the difference in their transcriptome profile. The data here presents the distinct molecular signatures present in each stage of neutrophil development and the factors required for each stage of development.
2018-02-23 | GSE109467 | GEO