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在单个缺血性人类心脏心肌细胞的体基因组和转录基因组变化
Nazia Hilal1,2,3, Zheming An1,2,3, Maksymilian Prondzynski2,4
1Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Research square
|February 20, 2025
概括
缺血性心脏病 (IHD) 损害心脏肌肉细胞,增加DNA突变和改变基因表达. 这项研究揭示了受IHD影响的心肌细胞中基因组和转录组变化的洞察力.
科学领域:
- 心脏病学 心脏病学
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 心力衰竭,特别是缺血性心脏病 (IHD),是全球死亡和住院的主要原因.
- IHD对心肌细胞基因组和转录组的影响尚不清楚.
- 心肌细胞随着年龄的增长而积累体质突变,这表明特定的细胞因素可能会影响这一过程.
研究的目的:
- 研究IHD对心肌细胞基因组和转录组的影响.
- 分析IHD心肌细胞中的体质DNA变异和基因表达模式.
- 了解IHD发展背后的分子机制.
主要方法:
- 来自人类左心室样本的单细胞全基因组和转录组数据的分析.
- 对5名心脏病患者和10名健康对照者的数据进行比较.
- 在体外研究使用诱导多能干细胞 (iPS) 衍生的缺氧心肌细胞.
主要成果:
- 在IHD心肌细胞中,体性DNA变异显著增加,具有明显的突变模式.
- 在IHD心肌细胞中的突变光谱表明DNA修复中断和细胞毒性环境.
- 转录组分析显示EGR1,FOS和原基因的表达增加,与心脏纤维化相关.
结论:
- IHD导致心肌细胞中DNA变化的异常积累.
- IHD心肌细胞的转录性变化有助于心脏纤维化.
- 这些基因组和转录基因组的改变为IHD的发病过程提供了关键的见解.
相关概念视频
Mutations
Overview
Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

