A dual genetic tracing system identifies diverse and dynamic origins of cardiac valve mesenchyme
A dual genetic tracing system identifies diverse and dynamic origins of cardiac valve mesenchyme
复制标题
双基因追踪系统识别心脏瓣膜间质的多样化和动态起源
DOI：
10.1242/dev.167775
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发表时间：
2018-09-01
期刊：
影响因子：
4.6
通讯作者：
Zhou, Bin
中科院分区：
文献类型：
--
作者：
Liu, Kuo;Yu, Wei;Zhou, Bin
摘要体内基因组工程是研究发育生物学和再生医学的重要手段。开发具有更多位点特异性重组酶（SSR）的新系统，与常用的Cre-loxP互补，对于更精确的谱系追踪和基因组编辑将是有价值的。在这里，我们通过Nigri-nox介绍一种新的SSR系统。通过产生组织特异性Nigri敲入及其响应的nox报告小鼠，我们表明Nigri-nox系统通过靶向特定组织在体内有效地工作。Nigri-nox作为Cre-loxP的一个新的正交体系，为遗传操作提供了额外的控制。我们还演示了如何两个正交系统Nigri-nox和Cre-loxP可以同时用于映射两个不同的发育起源的心脏瓣膜间充质在小鼠心脏的细胞命运，提供动态的细胞贡献从不同的起源心脏瓣膜间充质在发展过程中。这项工作提供了Nigri-nox系统在体内小鼠基因组工程中的原理验证应用。与其他SSR系统相结合，Nigri-nox将有助于更精确地描绘发育，疾病和再生过程中的起源和细胞命运。总结：Nigri-nox系统在体内小鼠基因组工程中的原理验证应用。
ABSTRACT In vivo genomic engineering is instrumental for studying developmental biology and regenerative medicine. Development of novel systems with more site-specific recombinases (SSRs) that complement with the commonly used Cre-loxP would be valuable for more precise lineage tracing and genome editing. Here, we introduce a new SSR system via Nigri-nox. By generating tissue-specific Nigri knock-in and its responding nox reporter mice, we show that the Nigri-nox system works efficiently in vivo by targeting specific tissues. As a new orthogonal system to Cre-loxP, Nigri-nox provides an additional control of genetic manipulation. We also demonstrate how the two orthogonal systems Nigri-nox and Cre-loxP could be used simultaneously to map the cell fate of two distinct developmental origins of cardiac valve mesenchyme in the mouse heart, providing dynamics of cellular contribution from different origins for cardiac valve mesenchyme during development. This work provides a proof-of-principle application of the Nigri-nox system for in vivo mouse genomic engineering. Coupled with other SSR systems, Nigri-nox would be valuable for more precise delineation of origins and cell fates during development, diseases and regeneration. Summary: A proof-of-principle application of the Nigri-nox system for in vivo mouse genomic engineering.