Muscle Organoids Reveal Exercise-Like Contractions Rapidly Promote Muscle Health Via Lamtor1's Signaling to Both AMPK and mTOR.

ABSTRACT: Exercise triggers molecular changes in skeletal muscles, but distinguishing immediate responses from secondary inter-organ interactions in muscle biopsies remains challenging. Here, this study differentiates human embryonic stem cells (hESCs) into induced skeletal muscle (iMusc) cells to identify hypertrophic factors and generates a novel 3D human iMusc organoid model for studying the direct effects of exercise-like contractions. Transcriptomics profiling reveals iMusc organoids rapidly induced genes associated with calcium signaling, p38/MAPK, EGF/ErbB, and NGF pathways within 1 h, mimicking exercise responses in vivo. Proteomics profiling and in vivo validation reveal rapid activation of both AMPK and mTORC1 signaling, partly through increased Lamtor1 levels, resolving a paradox in exerc

SUBMITTER: Yao Z 

PROVIDER: S-EPMC12752671 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature