脂肪組織におけるメゼンキマ原始細胞の階層の特定
David Merrick1,2, Alexander Sakers1,2, Zhazira Irgebay1,2
1Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|April 27, 2019
まとめ
代謝の健康は新しい脂肪細胞に 分化する脂肪組織の原始細胞に依存しています 研究者は特定の原始細胞の種類と 脂肪組織の発達と調節におけるその役割を特定しました
科学分野:
- 細胞生物学
- 代謝 健康
- アディポゲネシス
背景:
- 代謝の健康はデノボアディポゲネシス (de novo adipogenesis) に大きく依存し,この過程で脂肪組織の原始細胞が成熟したアディポサイトに微分化します.
- 精密な細胞階層とアディポサイトの祖先の分化を制御する規制メカニズムは,まだ完全に理解されていません.
- これらのプロセスを理解することは,脂肪組織機能の障害に関連する代謝障害に対処するために不可欠です.
研究 の 目的:
- マウスとヒトの両方の脂肪組織における脂肪細胞祖先の細胞階層と分化経路を解明する.
- アディポサイトの祖先の結合と分化に関与する重要な細胞表面マーカーと分子調節物質を特定する.
- これらの祖先細胞を収容する reticular interstitiumの役割を調査する.
主な方法:
- 単細胞RNAシーケンシング (scRNA-seq) を用いて,脂肪組織の原始細胞のトランスクリプトミックプロフィールを分析した.
- ディペプチドルペプチダゼ-4 (DPP4) / CD26および細胞間粘着分子-1 (ICAM1) / CD54を含む細胞表面マーカーは,異なる祖先集団を特定するために使用されました.
- 変形成長因子β (TGF-β) のシグナル伝達経路は,原始細胞のアイデンティティと分化を調節する役割について調査されました.
主要な成果:
- scRNA-seqは,両方の種における脂肪組織原始体内の異なったメゼンキマ細胞階層を明らかにした.
- ディペプチジルペプチダゼ-4 (DPP4) / CD26を発現する細胞は,高度に増殖し,多効性プロジェニータとして特定されました.
- これらのDPP4+原始細胞は,ICAM1/CD54発現するコミットプレアディポサイトと,Clec11a/F3/CD142発現するアディポゲン細胞に微分化します.
- 変形成長因子βは,DPP4+の祖先のアイデンティティを維持し,アディポゲン結合を抑制することが判明しました.
- DPP4+の祖先は,新たに認識された組織空間である網膜間部に局所されました.
結論:
- 脂肪組織の祖先の分化は,特定の表面タンパク質によって特徴づけられた異なる細胞集団を含む定義された階層に従う.
- DPP4+細胞は,脂質組織の膨張と代謝の健康に不可欠な,網膜間隔に存在する主要な多能原産体です.
- TGF-βシグナル伝達は,原始細胞状態を維持し,代謝疾患の潜在的治療標的を提供するために重要な役割を果たします.
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