HCN4 dynamically marks the first heart field and conduction system precursors.
HCN4 dynamically marks the first heart field and conduction system precursors.
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HCN4 动态标记第一个心脏场和传导系统前体
DOI：
10.1161/circresaha.113.301588
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发表时间：
2013-08-02
影响因子：
20.1
通讯作者：
Evans SM
中科院分区：
文献类型：
--
作者：
Liang X;Wang G;Lin L;Lowe J;Zhang Q;Bu L;Chen Y;Chen J;Sun Y;Evans SM
基本原理：迄今为止，还没有第一心野的特异性标记物来帮助理解第一心野对心脏谱系的贡献。心律失常是死亡的主要原因，通常由心脏传导系统（CCS）异常引起。了解CCS谱系的起源和识别标志物是CCS疾病建模和生物起搏器开发的重要步骤。目的：研究HCN 4作为第一心野和CCS不同组分的前体的标志物，并深入了解第一和第二心脏谱系对CCS的贡献。方法和结果：产生HCN 4CreERT 2、-核LacZ和-H2 BGFP小鼠系。通过HCN 4抗体免疫染色和报告基因表达检测HCN 4表达。使用HCN 4CreERT 2、IsllCre、Nkx2.5Cre和Tbx 18 Cre进行谱系研究，并与CCS标记物的共免疫染色偶联。结果表明，在心脏新月体阶段，HCN 4标记第一心脏区域，HCN 4CreERT 2允许评估第一心脏区域肌细胞所采用的细胞命运。在整个胚胎发育过程中，HCN 4表达在不同阶段标记不同的CCS前体，在胎儿晚期标记整个CCS。我们还注意到HCN 4在特定发育阶段的不同内皮细胞亚群中的表达。结论：这项研究提供了深入了解第一和第二心脏谱系的CCS的贡献，并强调了潜在的使用HCN 4与其他标志物的优化协议的生成和隔离特定的传导系统前体。
Rationale: To date, there has been no specific marker of the first heart field to facilitate understanding of contributions of the first heart field to cardiac lineages. Cardiac arrhythmia is a leading cause of death, often resulting from abnormalities in the cardiac conduction system (CCS). Understanding origins and identifying markers of CCS lineages are essential steps toward modeling diseases of the CCS and for development of biological pacemakers. Objective: To investigate HCN4 as a marker for the first heart field and for precursors of distinct components of the CCS, and to gain insight into contributions of first and second heart lineages to the CCS. Methods and Results: HCN4CreERT2, -nuclear LacZ, and -H2BGFP mouse lines were generated. HCN4 expression was examined by means of immunostaining with HCN4 antibody and reporter gene expression. Lineage studies were performed using HCN4CreERT2, Isl1Cre, Nkx2.5Cre, and Tbx18Cre, coupled to coimmunostaining with CCS markers. Results demonstrated that, at cardiac crescent stages, HCN4 marks the first heart field, with HCN4CreERT2 allowing assessment of cell fates adopted by first heart field myocytes. Throughout embryonic development, HCN4 expression marked distinct CCS precursors at distinct stages, marking the entire CCS by late fetal stages. We also noted expression of HCN4 in distinct subsets of endothelium at specific developmental stages. Conclusions: This study provides insight into contributions of first and second heart lineages to the CCS and highlights the potential use of HCN4 in conjunction with other markers for optimization of protocols for generation and isolation of specific conduction system precursors.