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

Harmandeep Kaur; J Carvalho; M Looso; P Singh; R Chennupati; J Preussner; S Günther; J Albarrán-Juárez; D Tischner; S Classen; S Offermanns; N Wettschureck

doi:10.1038/ncomms15700

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

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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.

Originalsprog	Engelsk
Artikelnummer	15700
Tidsskrift	Nature Communications
Vol/bind	8
Sider (fra-til)	15700
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms15700
Status	Udgivet - 16 jun. 2017
Udgivet eksternt	Ja

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Kaur, H., Carvalho, J., Looso, M., Singh, P., Chennupati, R., Preussner, J., Günther, S., Albarrán-Juárez, J., Tischner, D., Classen, S., Offermanns, S., & Wettschureck, N. (2017). Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system. Nature Communications, 8, 15700. Artikel 15700. https://doi.org/10.1038/ncomms15700

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

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.",

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AU - Kaur, Harmandeep

AU - Carvalho, J

AU - Looso, M

AU - Singh, P

AU - Chennupati, R

AU - Preussner, J

AU - Günther, S

AU - Albarrán-Juárez, J

AU - Tischner, D

AU - Classen, S

AU - Offermanns, S

AU - Wettschureck, N

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N2 - 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.

AB - 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.

KW - Animals

KW - Aorta/pathology

KW - Atherosclerosis/metabolism

KW - Cell Differentiation

KW - Cluster Analysis

KW - Exons

KW - Green Fluorescent Proteins/metabolism

KW - Humans

KW - Inflammation

KW - Ligands

KW - Mice

KW - Mice, Inbred C57BL

KW - Myocytes, Smooth Muscle/cytology

KW - Real-Time Polymerase Chain Reaction

KW - Receptors, G-Protein-Coupled/metabolism

KW - Sepsis/metabolism

KW - Single-Cell Analysis

KW - Tissue Array Analysis

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DO - 10.1038/ncomms15700

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SP - 15700

JO - Nature Communications

JF - Nature Communications

M1 - 15700

ER -

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

Abstract

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