Altering metabolism programs cell identity via NAD+- dependent deacetylation

ABSTRACT: Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures. This shift in cellular identity depends on inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS) triggered by replacement of D-glucose by D-galactose in ESC media. Enhanced OXPHOS in turn activates NAD+-dependent deacetylases of the sirtuin family, resulting in deacetylation of histones and key transcription factors to focus enhancer activity while reducing transcriptional noise, that resu

SUBMITTER: Joshua, Mark Brickman 

PROVIDER: S-SCDT-10_1038-S44318-025-00417-0 | biostudies-other |

REPOSITORIES: biostudies-other