Gaspar Ludmila, Brown Steven A
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Methods Enzymol. 2015;552:231-56. doi: 10.1016/bs.mie.2014.10.023. Epub 2015 Jan 10.
Circadian clocks are present in most cells and are essential for maintenance of daily rhythms in physiology, mood, and cognition. Thus, not only neurons of the central circadian pacemaker but also many other peripheral tissues possess the same functional and self-sustained circadian clocks. Surprisingly, however, their properties vary widely within the human population. In recent years, this clock variance has been studied extensively both in health and in disease using robust lentivirus-based reporter technologies to probe circadian function in human peripheral cells as proxies for those in neurologically and physiologically relevant but inaccessible tissues. The same procedures can be used to investigate other conserved signal transduction cascades affecting multiple aspects of human physiology, behavior, and disease. Accessing gene expression variation within human populations via these powerful in vitro cell-based technologies could provide important insights into basic phenotypic diversity or to better interpret patterns of gene expression variation in disease.
昼夜节律时钟存在于大多数细胞中,对于维持生理、情绪和认知方面的日常节律至关重要。因此,不仅中枢昼夜节律起搏器的神经元,许多其他外周组织也拥有相同的功能性和自我维持的昼夜节律时钟。然而,令人惊讶的是,它们的特性在人群中差异很大。近年来,利用强大的基于慢病毒的报告技术,在健康和疾病状态下广泛研究了这种时钟差异,以探测人类外周细胞中的昼夜节律功能,作为神经和生理相关但难以触及的组织中细胞的替代物。相同的程序可用于研究影响人类生理、行为和疾病多个方面的其他保守信号转导级联反应。通过这些强大的基于体外细胞的技术来获取人群中的基因表达变异,可为深入了解基本表型多样性或更好地解释疾病中的基因表达变异模式提供重要见解。