AMPK activation by glycogen expenditure primes the exit of naive pluripotency.

ABSTRACT: Embryonic and epiblast stem cells in pre-and post-implantation embryos are characterized by their naïve and primed states, respectively which represent distinct phases of pluripotency. Thus, cellular transition from naïve-to-primed pluripotency recapitulates a drastic metabolic and cellular remodeling after implantation to adapt to changes in extracellular conditions. Here, we found that inhibition of AMPK occurs during naïve transition with two conventional inhibitors of the MEK1 and GSK3β pathways. The accumulation of glycogen due to iGSK3β is responsible for AMPK inhibition, which accounts for high de novo fatty acid synthesis in naïve (ESCs). The knockout of glycogen synthase 1 in naïve ESCs; GKO, resulting in a drastic glycogen loss, leads to a robust AMPK activation and lowers the le

SUBMITTER: Kim SM 

PROVIDER: S-EPMC11933299 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature