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一种新型转基因 Cre 等位基因,用于标记小鼠心脏传导系统。

A novel transgenic Cre allele to label mouse cardiac conduction system.

机构信息

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, 8091, Switzerland.

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.

出版信息

Dev Biol. 2021 Oct;478:163-172. doi: 10.1016/j.ydbio.2021.07.005. Epub 2021 Jul 8.

Abstract

The cardiac conduction system is a network of heterogeneous cell population that initiates and propagates electric excitations in the myocardium. Purkinje fibers, a network of specialized myocardial cells, comprise the distal end of the conduction system in the ventricles. The developmental origins of Purkinje fibers and their roles during cardiac physiology and arrhythmia have been reported. However, it is not clear if they play a role during ischemic injury and heart regeneration. Here we introduce a novel tamoxifen-inducible Cre allele that specifically labels a broad range of components in the cardiac conduction system while excludes other cardiac cell types and vital organs. Using this new allele, we investigated the cellular and molecular response of Purkinje fibers to myocardial injury. In a neonatal mouse myocardial infarction model, we observed significant increase in Purkinje cell number in regenerating myocardium. RNA-Seq analysis using laser-captured Purkinje fibers showed a unique transcriptomic response to myocardial infarction. Our finds suggest a novel role of cardiac Purkinje fibers in heart injury.

摘要

心脏传导系统是一种异质细胞群体网络,它在心肌中引发和传播电兴奋。浦肯野纤维是一种特殊的心肌细胞网络,构成了心室传导系统的远端。浦肯野纤维的发育起源及其在心脏生理和心律失常中的作用已有报道。然而,目前尚不清楚它们在缺血性损伤和心脏再生中是否发挥作用。在这里,我们介绍了一种新型的他莫昔芬诱导型 Cre 等位基因,该基因可特异性标记心脏传导系统中的广泛成分,同时排除其他心脏细胞类型和重要器官。利用这个新的等位基因,我们研究了浦肯野纤维对心肌损伤的细胞和分子反应。在新生小鼠心肌梗死模型中,我们观察到再生心肌中浦肯野细胞数量显著增加。使用激光捕获的浦肯野纤维进行 RNA-Seq 分析显示,浦肯野纤维对心肌梗死有独特的转录组反应。我们的发现表明心脏浦肯野纤维在心脏损伤中具有新的作用。

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