Plin2-mediated lipid droplet mobilization accelerates exit from pluripotency by lipidomic remodeling and histone acetylation.

ABSTRACT: Metabolic switch is critical for cell fate determination through metabolic functions, epigenetic modifications, and gene expression. However, the mechanisms underlying these alterations and their functional roles remain unclear. Here, we show that Plin2-mediated moderate lipid hydrolysis is critical for pluripotency of embryonic stem cells (ESCs). Upon exit from pluripotency, lipid droplet (LD)-associated protein Plin2 is recognized by Hsc70 and degraded via chaperone-mediated autophagy to facilitate LD mobilization. Enhancing lipid hydrolysis by Plin2 knockout promotes pluripotency exit, which is recovered by ATGL inhibition. Mechanistically, excessive lipid hydrolysis induces a dramatic lipidomic remodeling characterized by decreased cardiolipin and phosphatidylethanolamine, which trigge

SUBMITTER: Wu Y 

PROVIDER: S-EPMC9613632 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature