The mTORC1-eIF4F axis controls paused pluripotency

ABSTRACT: Mouse embryonic stem cells (mESCs) can self-renew indefinitely and maintain pluripotency. Inhibition of mechanistic target of rapamycin (mTOR) by the kinase inhibitor INK128 is known to induce paused pluripotency in mESCs cultured with traditional serum/LIF medium (SL), but the underlying mechanisms remain unclear. In this study, we demonstrate that mTOR complex 1 (mTORC1) but not complex 2 (mTORC2) mediates mTOR-inhibition induced paused pluripotency in cells grown in both SL and 2iL medium (GSK3- and MEK-inhibitors and LIF). We also show that mTORC1 regulates self-renewal in both conditions mainly through eIF4F-mediated translation initiation that targets mRNAs of both cytosolic and mitochondrial ribosome subunits. Moreover, inhibition of mitochondrial translation is sufficient to induce

SUBMITTER: Ms. Xueting Xu 

PROVIDER: S-SCDT-EMBOR-2021-53081-T | biostudies-other |

REPOSITORIES: biostudies-other