Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system
H Kaur1, J Carvalho1, M Looso2
1Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstr 43, 61231 Bad Nauheim, Germany.
Nature Communications
|June 17, 2017
Summary
Single-cell analysis reveals diverse G-protein-coupled receptor (GPCR) expression in vascular cells. This heterogeneity impacts cell function and disease, offering new therapeutic targets for vascular diseases.
Area of Science:
- Vascular Biology
- Cellular Signaling
- Genomics
Background:
- G-protein-coupled receptor (GPCR) expression is crucial in vascular cell function.
- Bulk analysis methods obscure cell-specific GPCR heterogeneity.
- Understanding individual cell GPCR patterns is vital for vascular disease research.
Purpose of the Study:
- To investigate GPCR expression heterogeneity in single vascular smooth muscle cells (SMC) and endothelial cells (EC).
- To identify functional GPCR patterns associated with cell states and disease.
- To explore therapeutic targeting of specific GPCRs in vascular cells.
Main Methods:
- Microfluidic-based single-cell RNA sequencing.
- GPCR expression analysis in primary SMC and EC.
- Validation in reporter mice, protein analysis, and human cells.
- Analysis of murine models of sepsis and atherosclerosis.
Main Results:
- GPCR expression is highly heterogeneous across individual vascular cells.
- Inflammatory activation alters the GPCR repertoire in sepsis and atherosclerosis models.
- Dedifferentiating SMC upregulate specific GPCRs (e.g., Gpr39, Gprc5b, Gprc5c, Gpr124).
- Targeting Gprc5b influences SMC differentiation state.
Conclusions:
- Single-cell profiling reveals pathologically relevant GPCR subpopulations in vascular cells.
- Identified GPCR patterns provide insights into vascular disease mechanisms.
- This study lays the groundwork for novel therapeutic strategies targeting vascular diseases.
