Insights into cardiac conduction system formation provided by HCN4 expression.

Insights into cardiac conduction system formation provided by HCN4 expression.
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DOI:
10.1016/j.tcm.2014.08.009
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发表时间:
2015-01
影响因子:
9.3
通讯作者:
Sun Y
Sun Y
中科院分区:
医学2区
文献类型:
--
作者:
Liang X;Evans SM;Sun Y

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心脏传导系统(CCS)的特化肌细胞对于协调心房和心室的顺序收缩是必不可少的。CCS的异常可导致致命的心律失常,包括病窦综合征和心房或心室颤动。为了开发针对心律失常的未来疗法和再生医学,重要的是要了解CCS不同组分的形成和功能。对这种理解至关重要的是CCS特异性标志物的开发。在这篇综述中,我们简要地总结了现有的CCS标记物的小鼠模型,并专注于那些涉及超极化阳离子选择性核苷酸门控阳离子通道,HCN 4,选择性地标志着所有组件的专门CCS在成人心脏。然而,最近的研究表明,HCN 4在发育过程中的表达在心脏前体细胞中是高度动态的。这些研究为第一和第二心脏领域对肌细胞和传导系统谱系的贡献提供了见解,并提出了发育过程中特定传导系统前体分配的时机。总之,他们强调了HCN 4作为CCS不同组分在不同发育阶段的细胞表面标志物的实用性,其可用于促进小鼠和人类模型系统中CCS前体的纯化和表征,并为再生疗法铺平道路。
Specialized myocytes of the cardiac conduction system (CCS) are essential to coordinate sequential contraction of cardiac atria and ventricles. Anomalies of the CCS can result in lethal cardiac arrhythmias, including sick sinus syndrome, and atrial or ventricular fibrillation. To develop future therapies and regenerative medicine aimed at cardiac arrhythmias, it is important to understand formation and function of distinct components of the CCS. Essential to this understanding is the development of CCS specific markers. In this review, we briefly summarize available mouse models of CCS markers, and focus on those involving the hyperpolarization cation-selective nucleotide gated cation channel, HCN4, which selectively marks all components of the specialized CCS in adult heart. Recent studies have revealed, however, that HCN4 expression during development is highly dynamic in cardiac precursors. These studies have offered insights into the contributions of the first and second heart field to myocyte and conduction system lineages, and suggested the timing of allocation of specific conduction system precursors during development. Altogether, they have highlighted the utility of HCN4 as a cell surface marker for distinct components of the CCS at distinct stages of development, which can be utilized to facilitate purification and characterization of CCS precursors in mouse and human model systems and pave the way for regenerative therapies.
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