線維芽細胞のインビトロ再プログラミングにより,多能なES細胞のような状態にします
Marius Wernig1, Alexander Meissner, Ruth Foreman
1Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Nature
|June 8, 2007
まとめ
科学者たちは,4つの転写因子を用いてマウスの線維芽細胞を誘発性多能幹細胞に再プログラムした. これらの細胞は,胚性幹細胞と表遺伝学的に,機能的に区別がつかないので,再生医療の潜在性を示しています.
科学分野:
- 幹細胞生物学 幹細胞生物学
- エピジェネティクス エピジェネティクス
- ゲノム再プログラミング
背景:
- 核移植は,体ゲノムを胚性表遺伝子状態に戻し,クローン動物や多能幹細胞を可能にします.
- 患者特有の胚性幹細胞 (ESCs) は治療的可能性を秘めているが,技術的,倫理的な障壁に直面している.
- 誘発性多能幹細胞 (iPSC) は,Oct4,Sox2,c-Myc,Klf4の産外発現を通じて,線維芽細胞から生成することができる.
研究 の 目的:
- インビトロ再プログラムされた誘発性多能幹細胞の表遺伝的状態と生物学的効能を調査する.
- マウスの線維芽細胞から生成されたiPSCを,マウスのES細胞と比較する.
主な方法:
- Oct4,Sox2,c-Myc,Klf4.4の子宮外発現を用いた線維細胞の再プログラム
- DNAメチル化,遺伝子発現,クロマチンの状態の分析.
- キメラ形成とテトラプロイド補完アッセイによる発達の可能性の評価.
主要な成果:
- 再プログラムされたiPSCは,ES細胞に匹敵するDNAメチル化,遺伝子発現,クロマチンの状態を示した.
- これらのiPSCは,成功裏に生存可能なキメラを形成し,生殖系統に寄与しました.
- 注射されたiPSCは,テトラプロイド補充に使用されたときに,生きた後期胚を生成しました.
結論:
- インビトロ再プログラムされたiPSCは,ES細胞と比較して区別がつかない生物学的効能と表遺伝的状態を有します.
- この再プログラミング方法は,再生医療と疾患モデリングに大きな期待を寄せている.
- この発見は,iPSCを治療用途でES細胞の有効な代替品として検証しています.
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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).
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01:24Methods of Nuclear Reprogramming
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