Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta
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 b...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52690 |
| _version_ | 1828376256307003392 |
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| author | Eric Engelbrecht Michel V Levesque Liqun He Michael Vanlandewijck Anja Nitzsche Hira Niazi Andrew Kuo Sasha A Singh Masanori Aikawa Kristina Holton Richard L Proia Mari Kono William T Pu Eric Camerer Christer Betsholtz Timothy Hla |
| author_facet | Eric Engelbrecht Michel V Levesque Liqun He Michael Vanlandewijck Anja Nitzsche Hira Niazi Andrew Kuo Sasha A Singh Masanori Aikawa Kristina Holton Richard L Proia Mari Kono William T Pu Eric Camerer Christer Betsholtz Timothy Hla |
| author_sort | Eric Engelbrecht |
| collection | DOAJ |
| description | 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 NFκB 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/ß-arrestin coupling. In contrast, circulatory S1P-dependent S1PR1/ß-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. |
| first_indexed | 2024-04-14T07:57:19Z |
| format | Article |
| id | doaj.art-2b95d8d5a479422885261efe96819fc7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:57:19Z |
| publishDate | 2020-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-2b95d8d5a479422885261efe96819fc72022-12-22T02:04:59ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.52690Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aortaEric Engelbrecht0Michel V Levesque1Liqun He2Michael Vanlandewijck3Anja Nitzsche4https://orcid.org/0000-0003-0567-6790Hira Niazi5Andrew Kuo6Sasha A Singh7Masanori Aikawa8https://orcid.org/0000-0002-9275-2079Kristina Holton9Richard L Proia10https://orcid.org/0000-0003-0456-1270Mari Kono11https://orcid.org/0000-0003-2447-4350William T Pu12https://orcid.org/0000-0002-4551-8079Eric Camerer13https://orcid.org/0000-0002-6271-7125Christer Betsholtz14Timothy Hla15https://orcid.org/0000-0001-8355-4065Vascular Biology Program, Boston Children's Hospital, Deapartment of Surgery, Harvard Medical School, Boston, United StatesVascular Biology Program, Boston Children's Hospital, Deapartment of Surgery, Harvard Medical School, Boston, United StatesDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Karolinska Institutet, Huddinge, SwedenDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Karolinska Institutet, Huddinge, SwedenUniversité de Paris, INSERM U970, Paris Cardiovascular Research Center, Paris, FranceUniversité de Paris, INSERM U970, Paris Cardiovascular Research Center, Paris, FranceVascular Biology Program, Boston Children's Hospital, Deapartment of Surgery, Harvard Medical School, Boston, United StatesCenter for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United StatesCenter for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United StatesHarvard Medical School Research Computing, Boston, United StatesGenetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United StatesGenetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United StatesDepartment of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, United StatesUniversité de Paris, INSERM U970, Paris Cardiovascular Research Center, Paris, FranceDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Karolinska Institutet, Huddinge, SwedenVascular Biology Program, Boston Children's Hospital, Deapartment of Surgery, Harvard Medical School, Boston, United StatesDespite 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 NFκB 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/ß-arrestin coupling. In contrast, circulatory S1P-dependent S1PR1/ß-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.https://elifesciences.org/articles/52690Sphingosine 1-phosphateendothelial cellschromatintranscriptomelymphatic endotheliumarterial endothelium |
| spellingShingle | Eric Engelbrecht Michel V Levesque Liqun He Michael Vanlandewijck Anja Nitzsche Hira Niazi Andrew Kuo Sasha A Singh Masanori Aikawa Kristina Holton Richard L Proia Mari Kono William T Pu Eric Camerer Christer Betsholtz Timothy Hla Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta eLife Sphingosine 1-phosphate endothelial cells chromatin transcriptome lymphatic endothelium arterial endothelium |
| title | Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta |
| title_full | Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta |
| title_fullStr | Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta |
| title_full_unstemmed | Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta |
| title_short | Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta |
| title_sort | sphingosine 1 phosphate regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta |
| topic | Sphingosine 1-phosphate endothelial cells chromatin transcriptome lymphatic endothelium arterial endothelium |
| url | https://elifesciences.org/articles/52690 |
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