全基因组对多能性路径的表征
Samer M I Hussein1, Mira C Puri2, Peter D Tonge1
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Nature
|December 16, 2014
概括
了解细胞重编程是关键. 这项研究揭示了细胞达到多能性的独特分子途径,受重编程因子水平和表观遗传变化的影响,导致不同的稳定细胞状态.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 表观遗传学和基因调控
- 干细胞生物学 干细胞生物学
背景情况:
- 在分子层面上,对体细胞重编程到多能性的理解仍然不完全.
- 在诱导多能性期间的动态变化缺乏全面的表征.
研究的目的:
- 提供从小鼠胚胎纤维细胞到诱导多能细胞的重编程过程的详细分子描述.
- 为了阐明在重编程过程中独特的基因表达,表观遗传特征和细胞命运.
主要方法:
- 产生广泛的转录基因组,表观基因组和蛋白质基因组数据集.
- 综合分析多学科数据,绘制重编程路线.
- 调查素H3素27三甲基化 (H3K27me3) 动态和DNA甲基化模式.
主要成果:
- 在重新编程过程中,细胞通过不同的分子状态过渡.
- 重编程分为转基因依赖和独立的多能状态.
- 早期事件涉及通过H3K27me3损失的染色质开放;转基因水平决定ESC类或替代多能命运的获取.
结论:
- 这项研究提供了体细胞重编程的全面分子路线图.
- 重编程结果对转录因子水平和表观遗传修饰很敏感.
- 数据可以通过Project Grandiose门户进行进一步研究.
相关概念视频
Combinatorial Gene Control
10.5K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
10.5K
Somatic to iPS Cell Reprogramming
2.9K
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...
2.9K
Induced Pluripotent Stem Cells
4.1K
4.1K
Induced Pluripotent Stem Cells
28.7K
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...
28.7K
Induced Pluripotent Stem Cells
6.4K
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...
Somatic...
6.4K
Chromatin Modification in iPS Cells
2.3K
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...
2.3K


