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ヒトの結腸直腸がんの単細胞マルチオミックシーケンシングと分析
Shuhui Bian1,2,3, Yu Hou1,2, Xin Zhou4
1Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China.
Science (New York, N.Y.)
|December 1, 2018
まとめ
この研究では,単細胞マルチオミクスを導入し,大腸がんのゲノム,エピジェノミク,およびトランスクリプトミクスのダイナミクスを分析します. DNA脱メチル化パターンはヘテロクロマチン密度と相関し,癌の進化に関する新しい洞察を提供します.
科学分野:
- 腫瘍学
- ゲノミクス
- エピジェネティクス
背景:
- 結腸直腸がん (CRC) は,ゲノム不安定性,表遺伝子異常,遺伝子発現不調によって特徴付けられています.
- 単細胞解像度でのこれらの特徴の同時分析は欠けている.
- CRCにおける腫瘍内異質性は,まだ完全に理解されていません.
研究 の 目的:
- 単細胞解像度で結腸直腸がんのゲノム,エピジェノミック,およびトランスクリプトミックの特徴を同時に分析する.
- 確立された概念を超えた腫瘍内異質性を調査する.
- 遺伝子系統を再構築し,その表遺伝子学と転写学的動態を追跡する.
主な方法:
- シングル・セル・マルチオミクス・シーケンス
- 原発性腫瘍,リンパ性腫瘍,遠隔転移の多領域採取
- ゲノム全体のDNAメチル化,H3K9me3ヒストンの改変,および遺伝子発現の分析.
主要な成果:
- ゲノム全体のDNAメチル化レベルは遺伝子サブライン内では一貫していました.
- 10人の患者で一貫した全ゲノムDNA脱メチル化パターンが観察されました.
- DNA脱メチル化の度合いは,ヘテロクロマチン関連H3K9me3と,長い間隔の核元素1密度と相関する.
結論:
- 単細胞マルチオミクス配列化は,大腸がんにおける遺伝系を再構築するために可能である.
- エピジェノミクスとトランスクリプトミクスダイナミクスは,これらの系統内で追跡できます.
- DNA脱メチル化パターンは,大腸がんの異質性と進化の洞察を提供します.
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