Wellcome Centre for Mitochondrial Research, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
NIHR Biomedical Research Centre, Faculty of Medical Science, Newcastle University, Newcastle, UK.
Sci Rep. 2024 Jun 14;14(1):13789. doi: 10.1038/s41598-024-64455-0.
Mitochondrial function is critical to continued cellular vitality and is an important contributor to a growing number of human diseases. Mitochondrial dysfunction is typically heterogeneous, mediated through the clonal expansion of mitochondrial DNA (mtDNA) variants in a subset of cells in a given tissue. To date, our understanding of the dynamics of clonal expansion of mtDNA variants has been technically limited to the single cell-level. Here, we report the use of nanobiopsy for subcellular sampling from human tissues, combined with next-generation sequencing to assess subcellular mtDNA mutation load in human tissue from mitochondrial disease patients. The ability to map mitochondrial mutation loads within individual cells of diseased tissue samples will further our understanding of mitochondrial genetic diseases.
线粒体功能对于细胞的持续活力至关重要，并且是越来越多种人类疾病的重要贡献者。线粒体功能障碍通常是异质性的，通过在特定组织中的一部分细胞中线粒体 DNA（mtDNA）变体的克隆扩增来介导。迄今为止，我们对 mtDNA 变体克隆扩增动态的理解在技术上仅限于单细胞水平。在这里，我们报告了使用纳米活检进行人体组织的亚细胞采样，结合下一代测序来评估来自线粒体疾病患者的人体组织中的亚细胞 mtDNA 突变负荷。在病变组织样本的单个细胞内绘制线粒体突变负荷的能力将进一步加深我们对线粒体遗传疾病的理解。
