人类诱导的多能干细胞体内编码突变
Athurva Gore1, Zhe Li, Ho-Lim Fung
1Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|March 4, 2011
概括
诱导多能干细胞 (hiPS) 可以在重编程过程中获得遗传突变. 这些获得的遗传修饰,与表观遗传变化一起,需要基因查以获得安全的临床应用.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 干细胞研究 干细胞研究
背景情况:
- 定义的转录因子可以在表观遗传上将成年哺乳动物细胞重新编程成诱导多能干细胞 (hiPS).
- 在重编程后,单个核酸水平上的基因组完整性在很大程度上仍未被描述.
研究的目的:
- 研究诱导多能干细胞 (hiPS) 在重编程过程中是否会获得遗传修饰.
- 评估通过不同的方法生成的hiPS细胞系中点突变的性质和频率.
主要方法:
- 使用五种不同的重编程方法生成的22个人类诱导多能干细胞 (hiPS) 细胞系的测序.
- 对点突变的蛋白质编码区域的分析,包括非同义,无意义和拼接变体.
- 将hiPS细胞的突变与它们的原始纤维细胞原生细胞进行比较.
主要成果:
- 在hiPS细胞系中,每个外体中平均发现了5个蛋白质编码点突变.
- 突变丰富了与癌症相关的基因.
- 大约一半的观察到的突变在原始细胞中已经存在,而其余的突变是在重编程期间或之后出现的.
结论:
- 人类诱导的多能干细胞 (hiPS) 除了经历表观遗传重编程外,还会获得遗传突变.
- 这些遗传变化可能包括与癌症相关的基因中的潜在有害变异.
- 在临床使用之前,全面的基因查对于确保hiPS细胞的安全至关重要.
相关概念视频
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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...
Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...
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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
iPS Cell Differentiation
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.


