The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition [CUT&Tag]

Inhibition of mTORC1 induces embryonic stem cells (ESCs) entry into a paused state which reversibly arrests self-renewal leaving pluripotency intact.

Hyperactivation of mTORC1 impedes both pluripotency re-establishment and exit of PSCs. As shown that mTORC1 mediates TFE3 nuclear translocation block pluripotency exit, whether similar mechanisms through transcription factor TFE3 are involved in these processes, and the detailed mechanism by which mTORC1-TFE3 regulates critical transcriptional processes for these transitions, remain unclear. In this study, we demonstrate that the nuclear translocation of TFE3, induced by hyperactivation of mTORC1, results in its binding to the nucleosome remodeling and deacetylation (NuRD) complex in both re-establishment and exit of pluripotency.