動脈硬化における幹細胞の増殖は,クローン細胞形成を加速する

Alexander Heyde¹, David Rohde², Cameron S McAlpine²

¹Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.

Cell

|February 26, 2021

まとめ

血液形成幹細胞の増殖はクローン細胞形成を加速し,心血管疾患のリスクを高めます. この研究は,動脈硬化症患者の幹細胞分裂率が上昇していることを明らかにし,この関連性の重要な部分を説明しています.

科学分野:

血液学
心血管科学
遺伝学

背景:

変異した造血幹細胞の複製であるクローン造血は,心血管疾患 (CVD) と関連しています.
クローナル血液形成とCVDを結びつけるメカニズムは不明である.

研究の目的:

血管新生幹細胞 (HSC) の増殖がCVDとクローン細胞形成の関連性を調査する.
HSCの分裂率の増加が動脈硬化症におけるクローン膨張に寄与するかどうかを判断する.

主な方法:

動脈硬化症のマウスとヒトにおけるHSC分裂率の測定
クロンの進化に及ぼす影響を評価するための数学的モデルを開発した.
Tet2欠乏性HSC移植による動脈硬化と睡眠の断片化のマウスモデルを用いて検証された結果

主要な成果:

動脈硬化症の患者およびマウスの場合,HSC分裂率は上昇しています.
数学的モデリングは増殖が体進化とクローン拡大を加速することを示しています
70歳までにクローナル血液形成のリスクが3. 5倍に増加することを予測しています.
血液形成活動が増加した状態で観測された Tet2- / - HSCの加速膨張.

結論:

HSCの増殖は,動脈硬化とクローン血液形成を結びつける重要なメカニズムです.
幹細胞分裂率の上昇は,CVDの文脈でクローナル血液形成の発生リスクに大きく寄与する.

キーワード:

動脈硬化症クロナル血液形成造血幹細胞ソマティック進化

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