Abstract
Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone marrow stromal cell types. Here we identified rare activated bone marrow monocytes and macrophages with high expression of α-smooth muscle actin (α-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs. These myeloid cells resisted radiation-induced cell death and further upregulated COX-2 expression under stress conditions. COX-2-derived prostaglandin E(2) (PGE(2)) prevented HSPC exhaustion by limiting the production of reactive oxygen species (ROS) via inhibition of the kinase Akt and higher stromal-cell expression of the chemokine CXCL12, which is essential for stem-cell quiescence. Our study identifies a previously unknown subset of α-SMA(+) activated monocytes and macrophages that maintain HSPCs and protect them from exhaustion during alarm situations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / immunology*
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Animals
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Bone Marrow / immunology*
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Bone Marrow / metabolism
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Bone Marrow / radiation effects
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Cell Communication / genetics
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Cell Communication / immunology
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Cell Movement / genetics
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Cell Movement / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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Cell Survival / radiation effects
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Chemokine CXCL12 / genetics
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Chemokine CXCL12 / immunology
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / immunology
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Dinoprostone / biosynthesis
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Dinoprostone / immunology
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Gamma Rays
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Gene Expression Regulation / immunology
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Gene Expression Regulation / radiation effects
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology*
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Hematopoietic Stem Cells / radiation effects
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Macrophages / cytology
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Macrophages / immunology*
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Macrophages / radiation effects
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / immunology
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Mesenchymal Stem Cells / radiation effects
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Mice
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Monocytes / cytology
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Monocytes / immunology*
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Monocytes / radiation effects
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / immunology
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Reactive Oxygen Species / immunology
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Reactive Oxygen Species / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology
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Signal Transduction / radiation effects
Substances
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Actins
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Chemokine CXCL12
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Cxcl12 protein, mouse
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Reactive Oxygen Species
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Proto-Oncogene Proteins c-akt
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Dinoprostone