昼間の分子時計は,表皮幹細胞の異質性を生み出します
Peggy Janich1, Gloria Pascual, Anna Merlos-Suárez
1Center for Genomic Regulation and UPF, 08003 Barcelona, Spain.
Nature
|November 15, 2011
まとめ
昼間の時計は,表皮幹細胞の活性化を調節する. この時計の障害は幹細胞の不均衡を引き起こし,早めの老化と腫瘍の発達の変化につながります.
科学分野:
- 幹細胞生物学 幹細胞生物学とは
- クロノバイオロジーはクロノバイオロジーを用います.
- 皮膚科 皮膚科について
背景:
- ネズミの表皮幹細胞は,組織再生のために休眠状態と活性化のサイクルを示します.
- 幹細胞の活性化は異質であり,細胞は異なる反応状態にある.
- ヘアフォリキュルの幹細胞のニッチは,逆の昼間相にある細胞を宿している.
研究 の 目的:
- 皮質幹細胞の異質性とホメオスタティックシグナルへの反応の調節における昼夜時計の役割を調査する.
- コアクロックタンパク質が幹細胞の活性化状態にどのように影響するかを決定する.
- サーカディアンクロックの障害が表皮の恒常性および腫瘍発生に与える影響を評価する.
主な方法:
- シルカディアン・クロック・リポーター・マウス・モデルを利用した.
- ヘアフォリクルニッチの幹細胞集団を分析した.
- 核の時計タンパク質Bmal1.1.による遺伝子発現の調節を調査した.
- Bmal1 (Arntl) またはPer1/2遺伝子を削除した結果について調べました.
主要な成果:
- 交差する昼間の相に並ぶ幹細胞集団は,休眠ニッチで特定されました.
- Bmal1の発現は振動し,活性化に先入観があるまたは活性化に弱い集団を生み出しました.
- Bmal1またはPer1/2の削除は,それぞれ幹細胞の蓄積または枯渇につながりました.
- 循環器の乱れは,表皮の早期老化を引き起こし,状腫瘍の発達を減少させた.
結論:
- 昼夜時計は,表皮幹細胞の時間的行動を正確に制御しています.
- 昼間の時計の乱れは,幹細胞ホメオスタシスを破壊する.
- 循環器時計の均衡は,腫瘍発生の傾向を調節する上で極めて重要です.
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