瘤中的单细胞mtDNA动态是由核和线粒体基因组的协同调节驱动的
Minsoo Kim1,2, Alexander N Gorelick2,3, Ignacio Vàzquez-García2
1Tri-Institutional PhD Program in Computational Biology & Medicine, Weill Cornell Medicine, New York City, NY, USA.
Nature genetics
|May 13, 2024
概括
瘤细胞显示线粒体DNA (mtDNA) 副本数的显著变化,与细胞大小和核DNA变化有关. 这种比率,而不仅仅是拷贝数量,影响细胞表型和适应性.
科学领域:
- 癌症生物学 癌症生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 瘤线粒体DNA (mtDNA) 拷贝数和基因型的细胞对细胞的变异性尚不清楚.
- 癌症中mtDNA变异的表型和进化影响尚不清楚.
研究的目的:
- 描述瘤mtDNA复制号和基因型的细胞对细胞变异.
- 研究癌细胞中mtDNA变异的表型和进化后果.
主要方法:
- 在72,275个单细胞上利用了无放大单细胞全基因组测序 (直接图书馆准备 (DLP+))
- 同时测试线粒体DNA (mtDNA) 复制号和核DNA (nuDNA).
- 通过单细胞RNA测序进行了多式分析.
主要成果:
- 观察到mtDNA拷贝数的广泛变化,与细胞大小有很强的相关性.
- 在nuDNA中发生的全基因组翻倍事件与mtDNA复制数的平衡适应有关.
- 鉴定了与mtDNA拷贝数和线粒体转录的异质体依赖性变化相关的mtDNA变异.
结论:
- mtDNA与nuDNA的比率,而不是单独的mtDNA拷贝数,调解了下游的表型.
- 现型性适应是由于核/线粒体平衡被破坏而产生的.
- 身体和生殖线mtDNA变异有助于改变线粒体功能和拷贝数.
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