SMAD3 and HIF-1α orchestrate metabolic transition to aerobic glycolysis as a critical prerequisite for spontaneous reprogramming of spermatogonial stem cells.

ABSTRACT: Spermatogonial stem cells (SSCs) possess the capacity for spontaneous reprogramming during in vitro culture, while the underlying mechanisms remain poorly understood, especially why the addition of epidermal growth factor (EGF), leukemia inhibitory factor (LIF) remarkably enhanced transition efficiency. Here we employed a multi-omics approach, integrating transcriptomics, metabolomics, and DNA methylation analyses to focus on the interplay between exogenous growth factors, metabolic pathways, and signaling cascades, particularly the role of SMAD3 in these networks. Our findings reveal that SSC reprogramming is contingent upon a metabolic shift from the tricarboxylic acid (TCA) cycle to aerobic glycolysis, modulated by fluctuating SMAD3 levels. SMAD3 downregulation activates HIF-1α, inducin

SUBMITTER: Cai Y 

PROVIDER: S-EPMC12305914 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature