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检测和测量 GPCR 信号——人诱导多能干细胞与永生化细胞系的比较。

Detecting and measuring of GPCR signaling - comparison of human induced pluripotent stem cells and immortal cell lines.

机构信息

Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, CA, United States.

Stanford Cardiovascular Institute, Stanford University, Stanford, CA, United States.

出版信息

Front Endocrinol (Lausanne). 2023 May 24;14:1179600. doi: 10.3389/fendo.2023.1179600. eCollection 2023.

Abstract

G protein-coupled receptors (GPCRs) are a large family of transmembrane proteins that play a major role in many physiological processes, and thus GPCR-targeted drug development has been widely promoted. Although research findings generated in immortal cell lines have contributed to the advancement of the GPCR field, the homogenous genetic backgrounds, and the overexpression of GPCRs in these cell lines make it difficult to correlate the results with clinical patients. Human induced pluripotent stem cells (hiPSCs) have the potential to overcome these limitations, because they contain patient specific genetic information and can differentiate into numerous cell types. To detect GPCRs in hiPSCs, highly selective labeling and sensitive imaging techniques are required. This review summarizes existing resonance energy transfer and protein complementation assay technologies, as well as existing and new labeling methods. The difficulties of extending existing detection methods to hiPSCs are discussed, as well as the potential of hiPSCs to expand GPCR research towards personalized medicine.

摘要

G 蛋白偶联受体(GPCRs)是一大类跨膜蛋白,在许多生理过程中发挥着重要作用,因此 GPCR 靶向药物的开发得到了广泛的推动。尽管永生化细胞系中的研究结果推动了 GPCR 领域的发展,但这些细胞系中 GPCR 的同质遗传背景和过表达使得难以将结果与临床患者相关联。人诱导多能干细胞(hiPSCs)有可能克服这些限制,因为它们包含患者特异性遗传信息,并可分化为多种细胞类型。为了在 hiPSCs 中检测 GPCRs,需要高度选择性的标记和敏感的成像技术。本综述总结了现有的共振能量转移和蛋白质互补测定技术,以及现有的和新的标记方法。讨论了将现有检测方法扩展到 hiPSCs 所面临的困难,以及 hiPSCs 在将 GPCR 研究扩展到个性化医疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa0/10244570/070d9cd6141f/fendo-14-1179600-g001.jpg

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