ヒトの膠芽細胞は,低レベルの原動力変異を有する腹腔下細胞から発生する
Joo Ho Lee1, Jeong Eun Lee1,2, Jee Ye Kahng1,3
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Nature
|August 3, 2018
まとめ
グリオブラストーマは,脳の下腹部 (SVZ) の神経幹細胞 (NSC) から発生します. これらの細胞は 誘導因子の変異を受け 移動し悪性グリオマを形成し GBM治療の新たな手段を 提供します
科学分野:
- 神経腫瘍学
- 癌 の 幹 細胞 生物学
- 遺伝学
背景:
- グリオブラストーマ (GBM) は,予後が悪い攻撃的な脳腫瘍です.
- GBMの起源細胞を特定することは,その発達と治療戦略を理解するために不可欠です.
- 以前の研究では,神経幹細胞 (NSC) が潜在的GBM起源であると示唆されたが,直接的な遺伝的証拠は欠けていた.
研究 の 目的:
- グリオブラストーマ (GBM) の起源細胞を,グリオマゲネシスの遺伝的基礎を調査することによって特定する.
- 特定の脳細胞とヒトの GBM 発症を直接的に関連付ける 分子遺伝的証拠を提供すること.
- ゲノム編集されたマウスモデルを使用して発見を検証する.
主な方法:
- 3回マッチした患者の組織 (正常なSVZ,腫瘍,正常な皮質/血液) の深層シーケンシング.
- 患者さんの脳組織の単細胞配列と レーザー微解剖
- GBMの発達を研究するためにマウスモデルでのゲノム編集.
主要な成果:
- IDHワイルド型GBM患者の56. 3%の正常なSVZ組織に低レベルのGBMドライバー変異が検出されました.
- これらの変異はマッチした腫瘍組織に高濃度で存在していた.
- ドライバ変異を携えたアストロサイトのようなNSCは,SVZから移住し,脳の遠くの領域でグリオマを引き起こすことが判明しました.
結論:
- アストロサイトのような神経幹細胞は,成人ヒトの腹腔下部領域に存在し,その細胞が芽細胞の起源である.
- これらの細胞は 誘導体変異を受け 高度悪性結晶腫を形成します
- この発見は,GBMの進行を理解し,新しい治療法を開発するための基本的な基礎を提供します.
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