ゲノム編集により,ヒトの胚形成におけるOCT4の役割が明らかになった
Norah M E Fogarty1, Afshan McCarthy1, Kirsten E Snijders2
1Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Nature
|September 28, 2017
まとめ
CRISPR-Cas9によるゲノム編集により,OCT4はヒトのブラストシスト発育に不可欠であることが明らかになりました. 人間の胚におけるOCT4 (POU5F1) 遺伝子編集は細胞運命を乱し,トロフェクトダームとエピブラストの両方の遺伝子発現に影響を与えます.
科学分野:
- 発達生物学
- 遺伝学
- 幹細胞生物学
背景:
- 人間の胚形成における 細胞運命を決定する初期段階は 極めて重要ですが 十分に理解されていません
- 転写因子OCT4は,多能性および早期発達において重要な役割を果たします.
研究 の 目的:
- CRISPR-Cas9によるゲノム編集を用いて,ヒトの胚形成中のOCT4の機能を調査する.
- ヒトのジゴットにおける効率的な遺伝子ターゲティングの方法を精錬する.
主な方法:
- CRISPR- Cas9 ゲノムエディティングは,二重体型ヒトのジゴートにおける POU5F1 遺伝子 (OCT4 をコードする) を標的とした.
- ヒトの胚性幹細胞とマウスのジゴットのマイクロインジェクションを用いて,効率的なOCT4 誘導RNAを特定した.
- トランスクリプトミクス分析はPOU5F1- nullヒト細胞で行われました.
主要な成果:
- ヒトの生殖細胞に POU5F1を標的とした場合 胚芽細胞の発達が損なわれます
- POU5F1-nullヒト細胞は,トロフェクトダーム (例えば,CDX2) とエピブラスト (例えば,NANOG) 遺伝子の抑制表現を示した.
- Pou5f1-nullのマウス胚は,破損した,しかし消滅していない,ブラストシストの発達と遺伝子発現を示した.
結論:
- CRISPR-Cas9によるゲノム編集は,ヒトの発達における遺伝子機能の研究に有効です.
- OCT4は,ヒト胚の適切な芽細胞発育と細胞運命を決定するのに不可欠です.
- 人間の発達におけるOCT4の役割は,マウスの発達における役割とは異なる.
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