Live-Cell Probe for In Situ Single-Cell Monitoring of Mitochondrial DNA Methylation,ACS Sensors

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Live-Cell Probe for In Situ Single-Cell Monitoring of Mitochondrial DNA Methylation
ACS Sensors ( IF 8.2 ) Pub Date : 2021-09-29 , DOI: 10.1021/acssensors.1c00731
Han Zhao ₁ , Donghan Ma _{1,

2} , Junkai Xie ₁ , Oscar Sanchez ₁ , Fang Huang _{2,

3} , Chongli Yuan _{1,

3}

Affiliation

Mitochondria, as the center of energy production, play an important role in cell homeostasis by regulating the cellular metabolism and mediating the cellular response to stress. Epigenetic changes such as DNA and histone methylation have been increasingly recognized to play a significant role in homeostasis and stress response. The cross-talking between the metabolome and the epigenome has attracted significant attention in recent years but with a major focus on how metabolism contributes to epigenomic changes. Few studies have focused on how epigenetic modifications may alter the mitochondrial composition and activity. In this work, we designed a novel probe targeting methylated CpGs of mitochondrial DNA (mtDNA). We demonstrated the capability of our probe to reveal the spatial distribution of methylated mtDNA and capture the mtDNA methylation changes at a single-cell level. We were also able to track single-cell mtDNA and nDNA methylation simultaneously and discovered the unsynchronized dynamics of the nucleus and mitochondria. Our tool offers a unique opportunity to understand the epigenetic regulation of mtDNA and its dynamic response to the microenvironment and cellular changes.

中文翻译：

用于线粒体 DNA 甲基化的原位单细胞监测的活细胞探针

线粒体作为能量产生的中心，通过调节细胞代谢和介导细胞对压力的反应，在细胞稳态中发挥重要作用。人们越来越多地认识到，DNA 和组蛋白甲基化等表观遗传变化在体内平衡和应激反应中发挥着重要作用。近年来，代谢组和表观基因组之间的交互引起了极大的关注，但主要关注代谢如何促进表观基因组的变化。很少有研究关注表观遗传修饰如何改变线粒体组成和活性。在这项工作中，我们设计了一种新型探针，靶向线粒体 DNA (mtDNA) 的甲基化 CpG。我们证明了我们的探针能够揭示甲基化 mtDNA 的空间分布并在单细胞水平捕获 mtDNA 甲基化变化。我们还能够同时跟踪单细胞 mtDNA 和 nDNA 甲基化，并发现细胞核和线粒体的不同步动态。我们的工具提供了一个独特的机会来了解 mtDNA 的表观遗传调控及其对微环境和细胞变化的动态响应。

更新日期：2021-10-22

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