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Chronic variable stress activates hematopoietic stem cells

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      Abstract

      Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis1,2. While incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known crosstalk between the brain and immune system includes the hypothalamic–pituitary–adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic–adrenal–medullary axis, which controls stress–induced catecholamine release in support of the fight–or–flight reflex3,4. It remains unknown however if chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive progenitors, giving rise to higher levels of disease–promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Sympathetic nerve fibers release surplus noradrenaline, which uses the β3 adrenergic receptor to signal bone marrow niche cells to decrease CXCL12 levels. Consequently, elevated hematopoietic stem cell proliferation increases output of neutrophils and inflammatory monocytes. When atherosclerosis–prone ApoE−/− mice encounter chronic stress, accelerated hematopoiesis promotes plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.

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      Most cited references 51

      • Record: found
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      Inflammation in atherosclerosis.

       Peter Libby (2015)
      Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The new appreciation of the role of inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies. Identifying the triggers for inflammation and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.
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        • Record: found
        • Abstract: not found
        • Article: not found

        A global measure of perceived stress.

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          • Record: found
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          Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.

          The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.
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            Author and article information

            Affiliations
            [1 ]Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge St., Boston, MA 02114, USA
            [2 ]Department of Cardiology and Angiology I, University Heart Center, Freiburg, Germany
            [3 ]Division of Psychiatry and Medicine, Massachusetts General Hospital
            [4 ]Benson–Henry Institute for Mind Body Medicine, Massachusetts General Hospital
            [5 ]Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
            [6 ]Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
            Author notes
            Corresponding author: Matthias Nahrendorf Center for Systems Biology 185 Cambridge Street Boston, MA 02114 Tel: (617) 643–0500 Fax: (617) 643–6133 mnahrendorf@ 123456mgh.harvard.edu
            Journal
            9502015
            8791
            Nat Med
            Nat. Med.
            Nature medicine
            1078-8956
            1546-170X
            2 June 2014
            22 June 2014
            July 2014
            01 January 2015
            : 20
            : 7
            : 754-758
            24952646
            4087061
            10.1038/nm.3589
            NIHMS595172
            Categories
            Article

            Medicine

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