线粒体捐赠技术是否会增加子代胎源性疾病的发生尚不清楚。线粒体－核的正常互作是个体正常发育的基本保障，但线粒体捐赠胚中线粒体与核的互作与对话尚未被涉足。课题组在前期研究中利用第一极体进行核置换的同时，采用线粒体疾病患者卵子胞浆补充法构建0%、5%、15%、30%线粒体异质性的胚胎，发现线粒体异质性程度影响线粒体捐赠胚的基因表达和甲基化状态；线粒体捐赠胚胎干细胞传代培养中，核供体来源的线粒体比例随干细胞代次上升，提示当存在两种线粒体时，核优先调控同源线粒体的复制和转录。因此，本项目将利用上述干细胞的传代培养追踪线粒体捐赠胚及干细胞中异源的核与线粒体之间的互作方式、两种线粒体的存在是否会影响核－线粒体的互作、表观遗传、细胞分化及功能等。对上述问题的揭示与阐明将绘制线粒体捐赠胚中核与线粒体的互作与对话网络、解答四种线粒体捐赠技术的安全性及有效性，为临床应用筛选出安全有效的线粒体捐赠方式，造福患者。

Whether mitochondria donation techniques will increase fetal origin disease remains unclear. Mitochondria-nuclear interaction is essential for individual development. However, it has not been involved in the Mitochondria-nuclear interaction in the Mitochondria donation embryos. In previous study, we built up embryos which contained 0%, 5%, 15%, and 30% heterogeneous mitochondria by patient ooplasm complement. It showed that the degree of mitochondria heterogeneity affected gene expression and methylation status of mitochondria donation embryos, and the percentage of the donated mitochondria increased with passage of embryonic stem cells derived from mitochondria donation embryos, suggesting the nucleus preferentially regulated replication and transcription of homologous mitochondria when there were two kinds of mitochondria. Therefore, based on embryonic stem cells above all, this project will follow up the interactions of heterogeneous mitochondria-nuclear in mitochondria donated embryo and embryonic stem cells, focus on whether the two kinds of mitochondria effect the interactions of mitochondria-nuclear, epigenetics status, cell differentiation and function, etc. The uncovering and clarification of these questions above all will draft the network of mitochondria-nuclear interactions, answer the efficacy and safety of three kinds of mitochondrial donated technology, and further select the most suitable mitochondrial donation ways to benefit patients.