ヒトの多能性幹細胞から採取した血液形成性幹細胞と原始細胞
Ryohichi Sugimura1,2,3,4, Deepak Kumar Jha1,2,3,4, Areum Han1,2
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|May 18, 2017
まとめ
研究者は多能性幹細胞から 機能的なヒト造血幹細胞を生成しました 7つの転写因子が同定され,血源性内皮を幹細胞と祖先細胞に変換し,多系統血球移植を可能にしました.
科学分野:
- 幹細胞生物学
- ヘマトポエシス
- 遺伝子調節
背景:
- 多能幹細胞は胚の発達を模倣して様々な組織に微分化することができる.
- 細胞の運命は,特定のマスター転写因子を表現することによって変化させることができる.
研究 の 目的:
- 多能幹細胞から機能するヒト造血幹細胞 (HSC) を生成する.
- HSCの発達と多系統移植を促進する重要な転写因子を特定する.
主な方法:
- ヒトの多能幹細胞を血球内皮に変異させる.
- HSCを特定する能力のための26の候補転写因子のスクリーニング
- マウスモデルにおける多線形造血移植の評価
主要な成果:
- 7つの転写因子 (ERG,HOXA5,HOXA9,HOXA10,LCOR,RUNX1,SPI1) が特定されました.
- これらの要因は,血源性内皮をHSCと原始細胞に変換した.
- 生成細胞は,マウスのプライマリーとセカンドリー受容体に,ミエロイド細胞,B細胞,T細胞を移植した.
結論:
- モルフォゲン分化と転写因子変換の組み合わせにより,多能幹細胞から機能的なHSCが得られます.
- この方法はヒト化したマウスの血液病のモデル化に 有望である.
- 遺伝的血液疾患の 治療的な応用の可能性
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