Horizontal mtDNA transfer between cells is common during mouse development.
Horizontal mtDNA transfer between cells is common during mouse development.
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DOI：
10.1016/j.isci.2022.103901
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发表时间：
2022-03-18
期刊：
影响因子：
5.8
通讯作者：
Mitalipov S
中科院分区：
文献类型：
--
作者：
Marti Gutierrez N;Mikhalchenko A;Ma H;Koski A;Li Y;Van Dyken C;Tippner-Hedges R;Yoon D;Liang D;Hayama T;Battaglia D;Kang E;Lee Y;Barnes AP;Amato P;Mitalipov S
在细胞分裂期间，细胞垂直地将它们的基因组传递给子细胞。在这里，我们展示了水平线粒体(Mt)DNA在不处于亲子关系的细胞之间的获取的发生和程度。由携带不同mtDNA单倍型的细胞组成的成年嵌合小鼠的不同组织和器官的广泛单细胞测序显示，相当一部分单个心肌细胞、神经元、神经胶质细胞、肠道和脾细胞捕获了高水平的供体mtDNA。此外，由野生型和突变型mtDNA组成的嵌合体显示野生型mtDNA向突变细胞的转运增加，这表明水平mtDNA转移可能是恢复受损线粒体功能的一种补偿机制。这些发现为进一步研究确定线粒体DNA供体细胞和转移机制奠定了基础，这些机制可能对开发新的基因疗法至关重要。成年小鼠单个细胞水平获得mtDNA供体心肌细胞、神经元和神经胶质细胞中异质供体的比例显著这些细胞中的mtDNA异质性可达50%致病的mtDNA突变可能增强野生型mtDNA的水平获得；细胞生物学；发育生物学
Cells transmit their genomes vertically to daughter cells during cell divisions. Here, we demonstrate the occurrence and extent of horizontal mitochondrial (mt)DNA acquisition between cells that are not in a parent-offspring relationship. Extensive single-cell sequencing from various tissues and organs of adult chimeric mice composed of cells carrying distinct mtDNA haplotypes showed that a substantial fraction of individual cardiomyocytes, neurons, glia, intestinal, and spleen cells captured donor mtDNA at high levels. In addition, chimeras composed of cells with wild-type and mutant mtDNA exhibited increased trafficking of wild-type mtDNA to mutant cells, suggesting that horizontal mtDNA transfer may be a compensatory mechanism to restore compromised mitochondrial function. These findings establish the groundwork for further investigations to identify mtDNA donor cells and mechanisms of transfer that could be critical to the development of novel gene therapies. Individual cells in adult mouse chimeras acquire donor mtDNA horizontally Significant percentage of cardiomyocytes, neurons, and glia were heteroplasmic Donor mtDNA heteroplasmy in these cells can reach up to 50% Pathogenic mtDNA mutations may potentiate horizontal acquisition of wild-type mtDNA Molecular biology; Cell biology; Developmental biology
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
4.7
作者：
Qin Y;Jiang X;Yang Q;Zhao J;Zhou Q;Zhou Y
通讯作者：
Zhou Y
DOI：
10.1038/nrg3275
发表时间：
2012-12
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.8
作者：
Lee HS;Ma H;Juanes RC;Tachibana M;Sparman M;Woodward J;Ramsey C;Xu J;Kang EJ;Amato P;Mair G;Steinborn R;Mitalipov S
通讯作者：
Mitalipov S
DOI：
10.1002/stem.2856
发表时间：
2018-09
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Hayakawa K;Chan SJ;Mandeville ET;Park JH;Bruzzese M;Montaner J;Arai K;Rosell A;Lo EH
通讯作者：
Lo EH