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ヒトゲノムにおける重要な遺伝子の識別と特徴付け

Tim Wang¹, Kıvanç Birsoy¹, Nicholas W Hughes²

¹Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.

Science (New York, N.Y.)

|October 17, 2015

まとめ

CRISPRスクリーンは癌細胞の生存と増殖に不可欠な遺伝子を特定しましたこれらのスクリーンは,根本的な経路,未定のRNA処理遺伝子,および細胞特有の本質性を明らかにし,がん細胞の責任識別のための戦略を提供しました.

科学分野:

ゲノミクス
分子生物学
癌研究

背景:

致命的なフェノタイプの大規模な遺伝分析は生物学的プロセスの分子基盤を明らかにします
バクテリアのクラスター化された定期的な間隔の短いパリンドロミック・リピート (CRISPR) システムは遺伝子スクリーニングの強力なツールです

研究の目的:

ヒトの癌細胞の増殖と生存に不可欠な遺伝子をゲノム全体のCRISPRスクリーンを用いて特定する.
オートホーガン方法による発見を検証し,異なる癌細胞系における重要な遺伝子セットを比較する.
細胞の重要なプロセス特にRNA処理に関与する未定の遺伝子を発見する

主な方法:

CRISPRスクリーニングのための全ゲノム単一ガイドRNAライブラリの構築.
ヒトの癌細胞系における増殖と生存に必要な遺伝子のスクリーニング
オートゴーナル遺伝子トラップベースのスクリーンを用いて検証し,酵母遺伝子ノックアウトと比較した.
複数の癌細胞系におけるCRISPRスクリーンの比較分析

主要な成果:

基本的経路の構成要素,高度に発現する遺伝子,そして少数の不活性化ポリモルフィズムを持つ細胞必須遺伝子のコアセットの識別.
RNA処理に関与する特異化されていない遺伝子の重要なグループが発見され,その一部が核細胞に局所化している.
癌の種類と細胞特性を反映した細胞特異の違いとともに,細胞系における遺伝子本質性の重複を示す.

結論:

CRISPRベースのスクリーンは癌細胞の重要な遺伝子を特定するのに強力です
特定された重要な遺伝子は基本的な細胞経路と潜在的な癌の危険性についての洞察を提供します
細胞特異的な遺伝子の重要性は,がんの異質性と,それに合わせた治療戦略の必要性を強調しています.

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