AQP5は幹細胞と胃の癌の起源を濃縮する

Si Hui Tan¹, Yada Swathi¹, Shawna Tan¹

¹A*STAR Institute of Medical Biology, Singapore, Singapore.

Nature

|February 7, 2020

まとめ

研究者らは,マウスとヒトの成人ピロリック幹細胞のマーカーとしてアクアポリン5 (AQP5) を特定した. この発見は胃がんの起源を理解し,胃幹細胞の再生医療を開発するのに役立ちます.

科学分野:

胃腸内科と腫瘍科
幹細胞生物学
分子生物学

背景:

LGR5はマウスのピロリック幹細胞を特定しますが,特定のマーカーがないため,ヒトの同位体は不明です.
LGR5+腸内幹細胞は,マウスのWNT誘発がんを誘発する;胃がんにおけるその役割は不明である.
WNT経路の調節障害はヒトの胃がんではよく見られる.

研究の目的:

ヒトとマウスの成人ピロリック幹細胞の表面マーカーを特定し,検証する.
WNTによる胃がんにおける特定された幹細胞の役割を調査する.
胃がんの発症とヒトの胃幹細胞の研究のための新しいモデルを確立する.

主な方法:

マウスの胃腸経路における LGR5+ 幹細胞集団の比較プロファイリング
幹細胞マーカーとしてのアクアポリン5 (AQP5) の機能的検証
Aqp5-creERT2 マウスモデルの生成 in vivoがん研究のために.
AQP5+細胞の腫瘍誘発能力を評価するために,in vitro オーガノイド培養

主要な成果:

AQP5はマウスとヒトの成人のピロリック幹細胞を豊かにするマーカーとして特定されました.
AQP5+幹細胞はWNT誘発の侵襲性胃がんを活かします
腫瘍に定着したAQP5+細胞は,選択的なオルガノイド開始を示し,がん幹細胞の可能性を示した.
AQP5の発現と局所化は,ヒトの胃がんサブタイプと転移で変化しています.

結論:

AQP5はマウスとヒトの成体ピロリック幹細胞の検証されたマーカーです.
AQP5でマークされたピロリック幹細胞は,WNT誘発の胃がんの源です.
特定されたマーカーとモデルは,胃がんの発達とヒトの胃幹細胞生物学の研究に不可欠です.
この研究は人間の胃の幹細胞を用いた再生医療への道を開きます

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