Reassessment of Isl1 and Nkx2-5 cardiac fate maps using a Gata4-based reporter of Cre activity.
Reassessment of Isl1 and Nkx2-5 cardiac fate maps using a Gata4-based reporter of Cre activity.
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DOI：
10.1016/j.ydbio.2008.08.013
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发表时间：
2008-11-01
影响因子：
2.7
通讯作者：
Pu, William T.
中科院分区：
文献类型：
--
作者：
Ma, Qing;Zhou, Bin;Pu, William T.
表达Isl1和Nkx2 - 5的心血管祖细胞在心脏发生过程中起着关键作用。先前报道的基于Cre的谱系追踪研究表明，Isl1祖细胞主要参与第二心脏区的衍生结构，而Nkx2 - 5祖细胞主要参与心肌细胞谱系。然而，Cre报告基因的部分重组会使Cre谱系追踪实验的结果解读变得复杂。我们发现，基于Gata4的Cre激活报告基因被Isl1Cre和Nkx2 - 5Cre重组的区域比先前使用标准Cre激活报告基因所报道的要广泛得多。扩展后的Isl1和Nkx2 - 5心脏谱系图谱非常相似，包括对所有四个心腔的心肌细胞、心内膜和平滑肌谱系的广泛贡献。这些数据表明，Isl1在第一和第二心脏区的祖细胞中均有表达，并且Nkx2 - 5除了在心肌细胞中表达外，还在心脏内皮和平滑肌的祖细胞中表达。这些结果对我们理解体内心脏谱系分化以及解读基于Cre的谱系图谱具有重要意义。
Isl1 and Nkx2–5 expressing cardiovascular progenitors play pivotal roles in cardiogenesis. Previously reported Cre-based fate mapping studies showed that Isl1 progenitors contribute predominantly to the derivatives of the second heart field, and Nkx2–5 progenitors contributed mainly to the cardiomyocyte lineage. However, partial recombination of Cre reporter genes can complicate interpretation of Cre fate mapping experiments. We found that a Gata4-based Cre-activated reporter was recombined by Isl1Cre and Nkx2–5Cre in a substantially broader domain than previously reported using standard Cre-activated reporters. The expanded Isl1 and Nkx2–5 cardiac fate maps were remarkably similar, and included extensive contributions to cardiomyocyte, endocardial, and smooth muscle lineages in all four cardiac chambers. These data indicate that Isl1 is expressed in progenitors of both primary and secondary heart fields, and that Nkx2–5 is expressed in progenitors of cardiac endothelium and smooth muscle, in addition to cardiomyocytes. These results have important implications for our understanding of cardiac lineage diversification in vivo, and for the interpretation of Cre-based fate maps.
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