在单细胞分辨率下解开肝细胞癌中不稳定的线粒体DNA突变的双向演变
Kaixiang Zhou1, Zhenni Wang1, Wenjie Guo1
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, China.
Hepatology (Baltimore, Md.)
|December 6, 2024
概括
这项研究揭示了肝癌细胞中线粒体DNA突变的独特模式,显示了不稳定的突变如何促进瘤进化和侵略. 了解这些单细胞动态为肝癌 (HCC) 的诊断和治疗提供了新的途径.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 线粒体DNA研究研究
背景情况:
- 线粒体DNA (mtDNA) 的体性突变在肝细胞癌 (HCC) 中普遍存在,并影响代谢平衡和瘤进展.
- 在mtDNA突变 (异质体) 中的细胞异质性在瘤发生中起作用,但其在单细胞分辨率下HCC中的进化动态尚未完全理解.
研究的目的:
- 系统地研究单细胞体质mtDNA突变格局和HCC的进化动态.
- 用单细胞分辨率来描述HCC中的内异质性 (ITH) 和克隆进化模式.
主要方法:
- 开发和应用基于单细胞捕获的mtDNA测序方法.
- 分析了来自11名HCC患者的1641个单细胞和来自2名患者衍生的异种移植小鼠模型的528个细胞.
- 进化历史的重建和时空谱系的追踪.
主要成果:
- 鉴定了两种类型的mtDNA突变:稳定和不稳定,基于异质体水平.
- 不稳定的mtDNA突变和高ITH之间的积极关联,与侵略性的HCC特征相关.
- 将HCC进化分类为线性或分支模式,有证据表明不稳定突变的双向进化.
结论:
- 这项研究阐明了HCC.中体质mtDNA突变的单细胞格局.
- 不稳定的mtDNA突变的双向进化是一个关键的发现,对HCC分层和治疗有影响.
相关概念视频
Animal Mitochondrial Genetics
7.5K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.5K
Mitochondrial Membranes
8.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
8.6K
Cancers Originate from Somatic Mutations in a Single Cell
11.6K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.6K
Mismatch Repair
4.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K


