Oct4 maintains the pluripotency of human embryonic stem cells by inactivating p53 through Sirt1-mediated deacetylation.

ABSTRACT: Oct4 is critical to maintain the pluripotency of human embryonic stem cells (hESCs); however, the underlying mechanism remains to be fully understood. Here, we report that silencing of Oct4 in hESCs leads to the activation of tumor suppressor p53, inducing the differentiation of hESCs since acute disruption of p53 in p53 conditional knockout (p53CKO) hESCs prevents the differentiation of hESCs after Oct4 depletion. We further discovered that the silencing of Oct4 significantly reduces the expression of Sirt1, a deacetylase known to inhibit p53 activity and the differentiation of ESCs, leading to increased acetylation of p53 at lysine 120 and 164. The importance of Sirt1 in mediating Oct4-dependent pluripotency is revealed by the finding that the ectopic expression of Sirt1 in Oct4-silenced

SUBMITTER: Zhang ZN 

PROVIDER: S-EPMC3947311 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature