Prox1増強剤はリンパ系血管の血液形成を抑制する
Jan Kazenwadel1, Parvathy Venugopal1,2, Anna Oszmiana1
1Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia.
Nature
|January 25, 2023
まとめ
リンパ内皮細胞のアイデンティティに不可欠なProx1遺伝子の発現を制御する新しい増強剤要素. マウスの体内におけるその障害は 深刻なリンパ系欠陥を引き起こし, リンパ系内皮の血球形成の隠された能力を明らかにした.
科学分野:
- 発達生物学
- 分子生物学
- 遺伝学
背景:
- トランスクリプション強化剤は,発達中の細胞のアイデンティティの遺伝子発現を制御する.
- Prox1はリンパ内皮細胞 (LEC) のアイデンティティの重要なレギュラーです.
研究 の 目的:
- LECにおけるProx1発現を調節する新しい増強剤を特定し,特徴づけること.
- リンパの発達と細胞の運命におけるこの増強剤の機能的役割を調査する.
主な方法:
- Prox1より上流で進化的に保存された新しい強化要素の特定.
- 転写因子結合部位 (GATA2,FOXC2,NFATC1,PROX1) の分析
- マウスにおけるGATA2結合部位を 破壊するゲノム編集
主要な成果:
- マウスでは,重度のリンパ系血管の欠陥により,増強剤の作用が妨げられ,生後死亡を引き起こした.
- 強化剤変異LECは,LEC特異遺伝子の発現が低下し,血液内皮関連遺伝子の発現が増加した.
- ミュータントマウスは リンパ内皮が血液形成細胞を生成する能力を示した.
結論:
- 新しい増強剤は,Prox1の発現を調節し,LECの同一性を維持するために不可欠です.
- リンパ内皮には潜伏した血液生成能力があり,通常はProx1によって抑制されます.
- この発見は,リンパ内皮細胞の発達可能性を再定義します.
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