胚性幹細胞の効能は,内生レトロウイルスの活動によって変動する.
Todd S Macfarlan1, Wesley D Gifford, Shawn Driscoll
1Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA.
Nature
|June 23, 2012
まとめ
研究者らはマウス培養で珍しい2細胞 (2C) のような幹細胞を発見した. これらの細胞は,典型的な多能幹細胞とは異なり,胚性および胚外組織の両方を形成することができ,早期発育と細胞運命を調節する新しい洞察を提供します.
科学分野:
- 発達生物学 発達生物学について
- 幹細胞生物学 幹細胞生物学
- ゲノミクスゲノミクスとは
背景:
- 胚性幹細胞 (ES) は,芽細胞から派生し,内部の細胞質に似ているが,すべての胚外組織を形成することはできない.
- ES細胞の多能性は,Oct4,Sox2,Nanog.のような特定のタンパク質マーカーと典型的に関連しています.
研究 の 目的:
- マウスESにおける希少細胞集団と,トーティポテンシャルを持つ誘発性多能幹細胞 (iPS) 細胞培養物を特定し,特徴づけること.
- この一時的なトーティポテンスのような状態を支配する分子機構と細胞ファート調節を調査する.
主な方法:
- ESとiPSの培養の中で稀な細胞の遺伝子タグ付け.
- プラリポテンシータンパク質発現の分析 (Oct4, Sox2, Nanog).
- 胚性および胚外組織への貢献の評価.
- 2C型細胞のトランスクリプトームシーケンシングとバイオインフォマティック分析.
- ヒストン修正酵素の役割に関する研究.
主要な成果:
- 2細胞 (2C) 胚トランスクリプトを発現する希少で一時的な細胞群がマウスのES細胞とiPS細胞で特定されました.
- これらの2C型細胞は,主要な多能性マーカー (Oct4,Sox2,Nanog) を欠いており,全能性を発揮し,胚性および胚外血統に寄与しています.
- ほぼすべてのES細胞は,ヒストン修飾酵素の影響で,このトーティポテンツのような状態をサイクルすることが観察されました.
- バイオ情報分析により,2Cトランスクリプトの多くは内生レトロウイルスの長い末端の繰り返しから発生し,細胞命運調節におけるその役割を示唆していることが明らかになった.
結論:
- 標準的なマウスESとiPSの細胞培養の中で,典型的な多能状態とは異なる,一時的なトーティポテントのような状態が存在します.
- この2Cのような状態は,表遺伝的要因と潜在的に内生的なレトロウイルス要素によって調節され,幹細胞の発達可能性を拡大します.
- この状態を理解することは,早期哺乳類の発達と再生医療の応用のための細胞運命の可塑性に関する新しい洞察を提供します.
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