m 6 A表观转录组修饰
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Cell Discovery:胡大海/申亮亮/宋保强等发现让人类脂肪干细胞“返老还童”的新策略
生物世界· 2026-01-26 07:00
Core Viewpoint - The study identifies IGF2BP3 as a key regulatory factor in the aging of human adipose-derived stem cells (hASC), linking m6A epitranscriptomic modifications with metabolic reprogramming, and establishes the IGF2BP3-m6A-BCAT1/GLS signaling axis as a potential therapeutic target for enhancing tissue regeneration in aged hASC [4][8]. Group 1 - Aging impairs the regenerative capacity and differentiation potential of human adipose-derived stem cells (hASC), but the underlying mechanisms remain unclear [2][6]. - The research demonstrates that IGF2BP3-dependent glutamine and branched-chain amino acid (BCAA) metabolic reprogramming rejuvenates aged hASC, enhancing their tissue regeneration capabilities [3][4]. - A metabolically active subpopulation of hASC, characterized by increased BCAA and glutamine metabolism, is primarily found in infant-derived hASC, indicating a link between metabolic activity and stem cell youthfulness [7]. Group 2 - The study reveals that the decline of the IGF2BP3-m6A-BCAT1/GLS signaling axis with age leads to functional deterioration in aged hASC [7][8]. - Rescue experiments indicate that restoring BCAT1/GLS or supplementing with BCAA/glutamine can significantly rejuvenate aged hASC, improving their proliferation, differentiation, and wound healing abilities [7][8]. - The research proposes two therapeutic strategies: nutritional supplementation to address metabolic deficiencies and m6A regulation to stabilize key mRNA, providing clinically feasible solutions for optimizing aged hASC for tissue regeneration [8].