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Updated: Jul 11, 2026
11:56
Generation of Mice Derived from Induced Pluripotent Stem Cells
Published on: November 29, 2012
产生具有生殖线能力的诱导多能干细胞
Keisuke Okita1, Tomoko Ichisaka, Shinya Yamanaka
1Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Nature
|June 8, 2007
概括
从小鼠纤维细胞生成诱导多能干细胞 (iPS细胞) 是可能的. 选择纳诺基表达产生的生殖线具有竞争力的iPS细胞,但c-Myc的重新激活对临床使用构成瘤风险.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 生殖生物学 生殖生物学
背景情况:
- 诱导多能干细胞 (iPS细胞) 是胚胎干细胞 (ES细胞) 的一个有希望的替代品.
- 以前使用Fbx15选择的方法产生了具有不完整发育潜力的iPS细胞和独特的表观遗传特征.
- 纳诺格在iPS细胞中实现充分多能性和生殖能力方面的作用需要进一步研究.
研究的目的:
- 为了调查是否选择Nanog表达在小鼠纤维细胞衍生的iPS细胞提高他们的多能性和生殖能力.
- 为了比较纳米选择的iPS细胞的基因表达和DNA甲基化模式与先前生成的Fbx15选择的iPS细胞.
- 评估纳米选择iPS细胞的体内发育潜力和安全性,特别是关于转基因沉默和瘤形成.
主要方法:
- 用Oct3/4,Sox2,c-Myc和Klf4.4对小鼠纤维细胞进行逆转录病毒转导.
- 基于Nanog表达的iPS细胞的选择.
- 对基因表达和DNA甲基化模式的分析.
- 测试瘤形成和奇美拉生成实验.
- 评估转基因沉默和后代的瘤发展.
主要成果:
- 与Fbx15选择的iPS细胞相比,纳米选择的iPS细胞在基因表达和DNA甲基化模式方面与ES细胞的相似性增加.
- 四个重编程转基因 (Oct3/4,Sox2,c-Myc,Klf4) 在纳米 iPS 细胞中被显著地沉默.
- 10个Nanog iPS细胞克隆中,有7个产生了成年嵌合体,其中一个克隆证明了生殖系传播.
- 在大约20%的后代中观察到瘤形成,这与c-Myc转基因的重新激活有关.
结论:
- 选择纳诺基表达是一种可行的策略,可以从小鼠纤维母细胞中产生生殖系相称的iPS细胞.
- 纳米选择的iPS细胞表现出改善的表观遗传和基因表达特征,类似于ES细胞.
- 虽然对再生医学有希望,但c-Myc的逆转录病毒输送需要谨慎,因为在临床应用中存在潜在的致癌风险.
相关概念视频
01:13Induced 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...
01:13Induced 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...
01:06Induced Pluripotent Stem Cells
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...
01:29Somatic to iPS Cell Reprogramming
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...
01:22iPS 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.