Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system.
Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system.
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DOI：
10.1038/ncomms15700
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发表时间：
2017-06-16
影响因子：
16.6
通讯作者：
Wettschureck N
中科院分区：
文献类型：
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作者：
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
G蛋白偶联受体（GPCR）的表达在大量的cDNA中被广泛研究，但在单个血管细胞中GPCR表达的异质性和功能模式知之甚少。在这里，我们在原代平滑肌细胞（SMC）和内皮细胞（EC）中进行基于微流体的单细胞GPCR表达分析。GPCR表达在所有细胞类型中是高度异质性的，这在报告小鼠中、在蛋白质水平上和在人细胞中得到证实。脓毒症或动脉粥样硬化的小鼠模型中的炎症激活导致GPCR库的特征性变化，并且我们鉴定了以特定GPCR模式为特征的功能相关的细胞亚群。我们进一步表明，去分化SMC上调GPCR，如Gpr39，Gprc5b，Gprc5c或Gpr124，Gprc5b的选择性靶向调节其分化状态。总之，单细胞分析鉴定了在病理相关亚群上表达的受体，并为血管疾病新治疗策略的开发提供了基础。GPCR是血管功能的关键调节因子。通过分析来自健康和患病鼠血管的血管平滑肌和内皮细胞中的单细胞GPCR表达，Kaur等人表明GPCR表达在所有细胞类型中是高度异质性的，并且疾病导致GPCR库变化，这取决于细胞类型和血管定位。
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, Kaur et 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.