Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta - Université Paris Cité Access content directly
Journal Articles eLife Year : 2020

Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta

Eric Engelbrecht
  • Function : Author
Michel V Levesque
  • Function : Author
Liqun He
  • Function : Author
Michael Vanlandewijck
  • Function : Author
Andrew Kuo
  • Function : Author
Sasha A Singh
  • Function : Author
Masanori Aikawa
Kristina Holton
  • Function : Author
Richard L Proia
Mari Kono
William T Pu
Eric Camerer
Christer Betsholtz
  • Function : Author
Timothy Hla

Abstract

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.
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Dates and versions

hal-03886150 , version 1 (06-12-2022)

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Eric Engelbrecht, Michel V Levesque, Liqun He, Michael Vanlandewijck, Anja Nitzsche, et al.. Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta. eLife, 2020, 9, ⟨10.7554/eLife.52690⟩. ⟨hal-03886150⟩

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