mTORの抑制は,一時的な多能状態を誘導する
Aydan Bulut-Karslioglu1, Steffen Biechele1, Hu Jin2,3
1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences and Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA.
Nature
|November 24, 2016
まとめ
ラパミシン (mTOR) の機械的標的の部分的阻害は,マウスブラストシストの可逆性多能幹細胞状態を誘導する. この発見は 再生医療と 発達のタイミングの理解に 新たな道を開きます
科学分野:
- 幹細胞生物学
- 発達生物学
- 生殖生物学
背景:
- 多能性幹細胞は再生医療にとって不可欠ですが,体内では一時的なものです.
- 胚性ダイアパウスは哺乳類の発達停止状態としてよく知られていない.
- ダイアパウスの制御を理解することは 発達のタイミングを制御する鍵です
研究 の 目的:
- ラパミシン (mTOR) のメカニスティック・ターゲットの役割について,ブラストシストの発達と多能性の調節について調査する.
- 新しい多能性幹細胞を特定し特徴づけること
- 再生医療と助産生殖への影響を調査する.
主な方法:
- マウスブラストシストと胚性幹細胞の培養におけるmTORの部分的抑制
- 発達停止,多能性,遺伝子発現の分析
- in vitro 停止したブラストシストと in vivo 停止したブラストシストの比較
主要な成果:
- mTORの部分的阻害は,マウスの芽細胞の発達を逆転的に停止し,長時間のex vivo培養を可能にします.
- 停止したブラストシストと培養された胚性幹細胞は多能性を維持し,生きた肥沃なマウスを生み出すことができます.
- ダイアパウズしたブラストシストとパウズしたブラストシストの両方が,mTORの活性,翻訳,および転写が低下しています.
結論:
- ダイアポーズされたブラストシストのエピブラストに似た新しい多能幹細胞の状態が特定されました.
- mTORシグナリングは,植え付近の段階での発達のタイミングを調節する.
- この発見は 助産生殖,再生医療,そして年齢関連の疾患に 影響を及ぼします
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