インテグリン経由のメカノシグナリングは,臓の祖先の運命決定を指示する
Anant Mamidi1, Christy Prawiro1, Philip A Seymour1
1Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark.
Nature
|November 30, 2018
まとめ
研究者らは細胞の形状と 細胞外マトリックス相互作用を制御することで 臓の原始細胞の運命を導いていることを発見しました この発見により,バイポテントな臓の祖先細胞がホルモン産生小島細胞に変換できる.
科学分野:
- 発達生物学
- 幹細胞生物学
- 細胞シグナリング
背景:
- 臓は前腸上皮の成長から発達し,多能の祖先を含んでいます.
- トランクドメインのバイポテンツ性臓原産細胞 (bi-PPs) は管と内分泌系に分離し,尖端原産細胞はアシナ細胞を形成する.
研究 の 目的:
- 臓の祖先細胞の運命決定を制御するシグナルメカニズムを特定する.
- 発達中の臓の 系統特異を制御する 外部と内部のシグナルを理解する
主な方法:
- ヒト胚性幹細胞由来胰腺バイ-PPの単細胞分析
- 細胞収束,細胞外マトリックス (ECM) の相互作用,およびF-アクチン-YAP1-ノッチのメカニカルシグナリング軸を調査するメカニズム研究.
主要な成果:
- 細胞の閉じ込めは内分泌の特異性を促進し 細胞の拡散は管状の運命を左右します
- ECM-インテグリンα5シグナリングは,管系統の分化を促進し,破壊は内分泌生成を刺激する.
- この経路の薬理学的または遺伝的障害は,bi-PPsをホルモン産生小島細胞に変換する.
結論:
- 細胞外的 (ECM) と内的な (メカノトランスデュークション) 経路は,bi-PPの運命決定のゲートキーパーとして機能する.
- この経路は,再生医療に意味を持つ,bi-PPから内分泌細胞を生成するために操作することができます.
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