幹細胞融合によって媒介される再プログラミングにはDNA合成が必要である
Tomomi Tsubouchi1, Jorge Soza-Ried, Karen Brown
1Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Cell
|February 19, 2013
まとめ
S/G2段階の胚性幹細胞 (ESC) は,体細胞の再プログラムを促進する. この多能性変換には,体核におけるDNA合成が不可欠であり,その決定的な役割を示している.
科学分野:
- 幹細胞生物学 幹細胞生物学とは
- エピジェネティクス エピジェネティクス
- 細胞を再プログラムする.
背景:
- 胚性幹細胞 (ESC) は,細胞融合を通じて,微分化した細胞に多能性を誘発することができる.
- この急速な再プログラミングの根本的なメカニズムは十分に理解されていません.
研究 の 目的:
- マウスESCの再プログラミング能力における細胞サイクルの役割を調査する.
- ESCによる体細胞の再プログラミング中の重要な分子イベントを特定する.
主な方法:
- マウスのESCを特定の細胞サイクル段階 (S/G2) で分離するための遠心分離.
- ヘテロカリアンおよびハイブリッドアッセイは,リンパ球および線維芽細胞の再プログラミングを評価するものです.
- BrdUパルスラベルとDNAポリメラーゼ阻害は,再プログラミング中のDNA合成を研究するために.
主要な成果:
- S/G2段階のESCでは,体細胞の再プログラムが強化されたことが示されました.
- 成功した再プログラミングは,体内核に早熟した核酸の組み込みと相関する.
- 再プログラムされている体内核は,融合後の24時間以内にBrdUを組み込みました.
- DNAポリメラーゼの活性抑制は,多能性変換を阻害しました.
結論:
- ESCの細胞サイクル段階は,その再プログラミングの可能性に影響を与える.
- ソマティック核における初期のDNA合成は,表遺伝的再プログラムにとって重要かつ不可欠な出来事である.
- 核酸の組み込みは,ESC-heterokaryons内の体細胞を再プログラムする重要な初期のステップです.
関連する概念動画
02:36DNA Damage can Stall the Cell Cycle
9.9K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.9K
01:24Methods of Nuclear Reprogramming
2.1K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.1K
01:14Introduction to Nuclear Reprogramming
2.2K
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
2.2K
01:29Somatic to iPS Cell Reprogramming
2.5K
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...
2.5K
01:32Chromatin Modification in iPS Cells
2.1K
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...
2.1K
02:31Homologous Recombination
62.2K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
62.2K