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

H. Kaur,J. Carvalho,M. Looso,P. Singh,Ramesh Chennupati,J. Preussner,S. Günther,J. Albarrán-Juárez,D. Tischner,S. Classen,S. Offermanns,N. Wettschureck

Published 2017 in Nature Communications

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. GPCRs are key regulators of vascular functions. By analysing single-cell GPCRs expression in vascular smooth muscle and endothelial cells from healthy and diseased murine vessels, Kauret al. show that GPCR expression is highly heterogeneous in all cell types and that disease causes GPCR repertoire changes depending on cell type and vascular localization.

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