単細胞マイクロコックヌクレアースの配列決定によって明らかになった核細胞組織の原理
Binbin Lai1, Weiwu Gao1,2, Kairong Cui1
1Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.
Nature
|September 28, 2018
まとめ
シングル・セル・マイクロコッカル・ヌクレアース・シーケンシング (scMNase-seq) は,細胞間でのニュクレオソームの位置づけとクロマチンのアクセシビリティの多様性を明らかにする. この新しい方法では 遺伝子活動と細胞の微分化能力と 関連した 異なる核細胞組織原理が 発見される.
科学分野:
- ゲノミクス
- エピジェネティクス
- 細胞生物学
背景:
- 核細胞の位置は染色体のアクセシビリティと遺伝子発現に影響する.
- 既存の方法は,細胞平均の核細胞プロファイルを提供し,細胞の異質性をマスクします.
- 遺伝子発現における細胞の異質性は,クロマチンのアクセシビリティの変動から生じる可能性があります.
研究 の 目的:
- 単細胞における全ゲノム・ワイド・ニュクレオソーム・ポジショニングとクロマチン・アクセシビリティの同時測定のための新しい技術を開発し,適用する.
- 核細胞組織の原理と遺伝子活動と細胞状態との関係を調査する.
- 細胞間でのクロマチン組織の変化を研究する.
主な方法:
- シングル・セル・マイクロコックヌクレアース配列化 (scMNase-seq) の開発
- scMNase-seqをNIH3T3細胞,マウスの初代CD4T細胞,マウスの胚性幹細胞に適用する.
- ゲノム全体の核細胞位置とクロマチンのアクセシビリティの解析
主要な成果:
- scMNase-seqは,2つの異なる核細胞組織原理を明らかにします.静寂/ヘテロクロマチン領域での高位置変異,および低位置変異の活性遺伝子/DNase I過敏領域での異質な間隔.
- DNase I過敏部位における核細胞間隔のバイモダル分布は,アクセシビリティ状態と細胞間変化と相関する.
- 細胞間よりも単細胞内での核群の多様性は低く,同じ細胞タイプ内での多様性は細胞間での多様性よりも低い.
- 不分化細胞は,分化のためのプライミングを示し,系統特有の強化剤で核細胞の占有量が減少しています.
結論:
- scMNase-seqは,単細胞核細胞組織とクロマチンのアクセシビリティに関する前例のない洞察を提供します.
- 核子の位置づけは,細胞型と遺伝子活動に依存する異質性を表している.
- 研究結果は,染色体アクセシビリティのパターンに基づいて,幹細胞とT細胞の予備された分化状態を明らかにしています.
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