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誘発された多能性への再プログラミングの表遺伝学
Bernadett Papp1, Kathrin Plath
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|March 19, 2013
まとめ
細胞を誘発性多能幹細胞 (iPSC) に再プログラムすることは,段階的な変化を伴う. 早期のエピジェネティック・プライミングは,後のプラリポテンシーに不可欠ですが,ヒトのiPSCにおけるX染色体の不安定性には注意が必要です.
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:
- 誘導性多能幹細胞 (iPSC) は,細胞の再プログラムによって生成されます.
- 再プログラミングは,転写とクロマチンの状態の変化を含む段階的なプロセスです.
- エピジェネティック改変は,再プログラミングの効率と結果において重要な役割を果たします.
研究 の 目的:
- 細胞がiPSCへと再プログラムされる段階的なメカニズムを解明する.
- プラリポテンシー誘導における早期のエピジェネティックイベントの重要性を強調する.
- このプロセスに対する再プログラミング因子と細胞外環境の影響を議論する.
主な方法:
- 再プログラミング因子結合と転写ダイナミクスの特徴.
- 再プログラミング中の染色体状態の変化の分析.
- エピジェネティック・プライミングイベントの調査.
主要な成果:
- 再プログラミング因子結合,転写,およびクロマチンの改変は,連続的に発生します.
- 早期のエピジェネティック・プライミング・イベントは,プラリポテンシー誘導の成功に不可欠である.
- 再プログラム因子レベル,ステキオメトリー,細胞外条件は,再プログラムの結果に大きな影響を与えます.
- 人間のiPSCにおけるX染色体の表遺伝的不安定性が確認されています.
結論:
- エピジェネティックダイナミクスを含む再プログラミングの段階的な性質を理解することは,iPSCアプリケーションの改善の鍵です.
- 新しい再プログラム因子カクテルの合理的な設計は,最近の進歩によって可能になっています.
- 人間のiPSCにおけるX染色体の発見された表遺伝的不安定性は,将来の研究と治療用途のために慎重に検討する必要があります.
関連する概念動画
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...
01:32Chromatin 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...
01:24Methods of Nuclear Reprogramming
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 injury repair.
01:14Introduction to Nuclear Reprogramming
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...
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...