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Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system

  • G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.

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Author:Harmandeep Kaur, Jorge CarvalhoORCiDGND, Mario LoosoORCiDGND, Pratibha Singh, Ramesh Chennupati, Jens PreussnerORCiDGND, Stefan GüntherORCiD, Julián Alberto Albarrán JuárezORCiDGND, Denise Tischner, Simon Classen, Stefan OffermannsORCiDGND, Nina Wettschureck
URN:urn:nbn:de:hebis:30:3-484276
DOI:https://doi.org/10.1038/ncomms15700
ISSN:2041-1723
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28621310
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/06/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/12/04
Tag:Atherosclerosis; Experimental models of disease; High-throughput screening; Reverse transcription polymerase chain reaction
Volume:8
Issue:Art. 15700
Page Number:15
First Page:1
Last Page:15
Note:
Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
HeBIS-PPN:440044669
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0