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腸内分泌レギュレータの特定 リアルタイム単細胞分化マッピング
Helmuth Gehart1, Johan H van Es2, Karien Hamer1
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Centre (UMC) Utrecht, 3584 CT Utrecht, the Netherlands.
Cell
|February 5, 2019
まとめ
腸内分泌細胞の分化を理解することが重要です この研究では 細胞の発達をリアルタイムでマッピングし 新しいレギュレータを特定し 細胞の種類が 時間の経過とともに変化する様子を明らかにしています
科学分野:
- 細胞生物学
- 発達生物学
- 胃腸内科
背景:
- 腸内分泌系統の恒常性調節は十分に理解されていない.
- 腸内分泌細胞は腸と脳のコミュニケーションと 代謝の調節に不可欠です
研究 の 目的:
- エントロエンドクリン分化中の転写変化を単細胞レベルでリアルタイムで解明する.
- 腸内分泌の階層とその亜系統の決定的な地図を作成する.
主な方法:
- 新しいNeurog3Chronoノックインアレルとバイ-光レポーターを使用して,時間解決の単細胞トランスクリプトミクスを用いた.
- マウスの条件付きノックアウトと腸内オルガノイドのCRISPR改変を用いて検証した.
主要な成果:
- 腸内分泌の階層と微分分化運動の決定的な記述を生成した.
- エントロクロマフィンとL細胞における時間依存のホルモン可塑性を明らかにした.
- 腸内分泌のフェノタイプに影響を与える6つの新規候補レギュレータ (Sox4,Rfx6,Tox3,Myt1,Runx1t1,Zcchc12) を特定し,検証した.
結論:
- 時間分解の単細胞転写マップは,腸内分泌の差異化の研究のための包括的なリソースを提供します.
- この研究は,腸内分泌細胞の発達を制御する重要な分子調節物質と動態を明らかにしています.
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