人間の誘発性多能幹細胞における体的コーディング変異
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
まとめ
誘発性多能幹細胞 (hiPS) は,再プログラム中に遺伝的変異を取得することができます. これらの得られた遺伝的変異は,表遺伝的変化とともに,安全な臨床応用のために遺伝的スクリーニングを必要とします.
科学分野:
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
- 幹細胞の研究について
背景:
- 定義された転写因子は,成人哺乳類の細胞をエピジェネティックに再プログラムして誘発性多能幹細胞 (hiPS) にすることができます.
- 再プログラミング後の単一ヌクレオチドレベルでのゲノム整合性は,主に特徴づけられていないままです.
研究 の 目的:
- 誘発性多能幹細胞 (hiPS) が再プログラミング過程で遺伝子改変を受けるか否かを調査する.
- 異なる方法によって生成されたhiPS細胞系における点変異の性質と頻度を評価する.
主な方法:
- 5つの異なる再プログラム方法を使用して生成された22人のヒト誘発多能幹細胞 (hiPS) 細胞の配列決定.
- 非同義,無意味,およびスプライス変異を含む点変異のためのタンパク質コーディング領域の分析.
- hiPS細胞の突然変異と,その元の線維芽細胞の祖先細胞の比較.
主要な成果:
- hiPSの細胞系では,エクソームあたり平均5つのタンパク質をコードする点変異が特定されました.
- 癌に関連する遺伝子に変異が濃縮された.
- 観察された突然変異の約半分は前身細胞に既に存在しており,残りの部分は再プログラム中に発生した.
結論:
- 人間の誘発性多能幹細胞 (hiPS) は,表遺伝的再プログラムに加えて,遺伝的変異も獲得する.
- これらの遺伝的変異には,がんに関連する遺伝子の潜在的に有害な変異が含まれます.
- 臨床使用前にhiPS細胞の安全性を確保するために,包括的な遺伝子スクリーニングが不可欠です.
関連する概念動画
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...
01:13Induced 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...
01:29Somatic 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...
01:22iPS 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.