IGF2BP3-dependent glutamine/BCAA metabolic rewiring rejuvenates aged human adipose-derived stem cells for enhanced tissue regeneration.

ABSTRACT: Aging impairs the regenerative capacity and differentiation potential of human adipose-derived stem cells (hASCs), but the mechanisms underlying their functional decline remain unclear. Through systematic functional assays and in vivo experiments, we first confirmed age-associated reductions in hASC self-renewal, lineage plasticity, and tissue repair efficacy. By integrating multiomics profiling and functional validation, we identified a metabolically active ACTA2⁺TAGLN⁺ subpopulation that was enriched mainly in infant-derived hASCs (I-hASCs) and characterized by increased catabolism of branched-chain amino acids (BCAAs) and glutamine. Mechanistically, the RNA-binding protein IGF2BP3, which is predominantly expressed in the ACTA2⁺TAGLN⁺ subpopula

SUBMITTER: Li Z 

PROVIDER: S-EPMC12819398 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature