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Sphingosine 1-phosp...
Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta
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- Engelbrecht, Eric (author)
- Harvard Med Sch, Dept Surg, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA
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- Levesque, Michel, V (author)
- Harvard Med Sch, Dept Surg, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA
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- He, Liqun (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Huddinge, Sweden
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- Vanlandewijck, Michael, 1982- (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Huddinge, Sweden
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- Nitzsche, Anja (author)
- Univ Paris, Paris Cardiovasc Res Ctr, INSERM U970, Paris, France
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- Niazi, Hira (author)
- Univ Paris, Paris Cardiovasc Res Ctr, INSERM U970, Paris, France
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- Kuo, Andrew (author)
- Harvard Med Sch, Dept Surg, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA
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- Singh, Sasha A. (author)
- Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Ctr Interdisciplinary Cardiovasc Sci, Boston, MA 02115 USA
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- Aikawa, Masanori (author)
- Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Ctr Interdisciplinary Cardiovasc Sci, Boston, MA 02115 USA
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- Holton, Kristina (author)
- Harvard Med Sch Res Comp, Boston, MA USA
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- Proia, Richard L. (author)
- NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA
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- Kono, Mari (author)
- NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA
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- Pu, William T. (author)
- Harvard Med Sch, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA;Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA
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- Camerer, Eric (author)
- Univ Paris, Paris Cardiovasc Res Ctr, INSERM U970, Paris, France
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, AstraZeneca Integrated Cardio Metab Ctr KI AZ ICM, Huddinge, Sweden
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- Hla, Timothy (author)
- Harvard Med Sch, Dept Surg, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA
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(creator_code:org_t)
- ELIFE SCIENCES PUBLICATIONS LTD, 2020
- 2020
- English.
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In: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 9
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- Despite the medical importance of G protein-coupled receptors (GPCRs), in vivo cellular heterogeneity of GPCR signaling and downstream transcriptional responses are not understood. We report the comprehensive characterization of transcriptomes (bulk and single-cell) and chromatin domains regulated by sphingosine 1-phosphate receptor-1 (S1PR1) in adult mouse aortic endothelial cells. First, S1PR1 regulates NF kappa B and nuclear glucocorticoid receptor pathways to suppress inflammation-related mRNAs. Second, S1PR1 signaling in the heterogenous endothelial cell (EC) subtypes occurs at spatially-distinct areas of the aorta. For example, a transcriptomically distinct arterial EC population at vascular branch points (aEC1) exhibits ligand-independent S1PR1/beta-arrestin coupling. In contrast, circulatory S1P-dependent S1PR1/beta-arrestin coupling was observed in non-branch point aEC2 cells that exhibit an inflammatory gene expression signature. Moreover, S1P/S1PR1 signaling regulates the expression of lymphangiogenic and inflammation-related transcripts in an adventitial lymphatic EC (LEC) population in a ligand-dependent manner. These insights add resolution to existing concepts of endothelial heterogeneity, GPCR signaling and S1P biology.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (subject category)
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eLIFE
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Engelbrecht, Eri ...
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Levesque, Michel ...
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He, Liqun
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Vanlandewijck, M ...
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Nitzsche, Anja
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Niazi, Hira
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Kuo, Andrew
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Singh, Sasha A.
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Aikawa, Masanori
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Holton, Kristina
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Proia, Richard L ...
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Kono, Mari
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Pu, William T.
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Camerer, Eric
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Betsholtz, Chris ...
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Hla, Timothy
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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eLIFE
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Uppsala University
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Karolinska Institutet