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

Author

Listed:
  • H. Kaur

    (Max Planck Institute for Heart and Lung Research)

  • J. Carvalho

    (Max Planck Institute for Heart and Lung Research)

  • M. Looso

    (ECCPS Bioinformatics Facility, Max Planck Institute for Heart and Lung Research)

  • P. Singh

    (Max Planck Institute for Heart and Lung Research)

  • R. Chennupati

    (Max Planck Institute for Heart and Lung Research)

  • J. Preussner

    (ECCPS Bioinformatics Facility, Max Planck Institute for Heart and Lung Research)

  • S. Günther

    (ECCPS Deep sequencing platform, Max Planck Institute for Heart and Lung Research)

  • J. Albarrán-Juárez

    (Max Planck Institute for Heart and Lung Research)

  • D. Tischner

    (Max Planck Institute for Heart and Lung Research)

  • S. Classen

    (Harvey Vascular Centre, Kerckhoff-Klinik)

  • S. Offermanns

    (Max Planck Institute for Heart and Lung Research
    Medical Faculty, J.W. Goethe University)

  • N. Wettschureck

    (Max Planck Institute for Heart and Lung Research
    Medical Faculty, J.W. Goethe University)

Abstract

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.

Suggested Citation

  • H. Kaur & J. Carvalho & M. Looso & P. Singh & R. Chennupati & J. Preussner & S. Günther & J. Albarrán-Juárez & D. Tischner & S. Classen & S. Offermanns & N. Wettschureck, 2017. "Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15700
    DOI: 10.1038/ncomms15700
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