Elevated p53 Activities Restrict Differentiation Potential of MicroRNA-Deficient Pluripotent Stem Cells.

ABSTRACT: Pluripotent stem cells (PSCs) deficient for microRNAs (miRNAs), such as Dgcr8^-/- or Dicer^-/- embryonic stem cells (ESCs), contain no mature miRNA and cannot differentiate into somatic cells. How miRNA deficiency causes differentiation defects remains poorly understood. Here, we report that miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8^-/- ESCs. Our data showed that miR-302 directly suppresses the tumor suppressor p53, which is modestly upregulated in Dgcr8^-/- ESCs and serves as a barrier restricting neural differentiation. We demonstrated that direct inactivation of p53 by SV40 large T antigen, a short hairpin RNA against Trp53, or genetic ablation of Trp53 in Dgcr8^-/- PSCs enables neural di

SUBMITTER: Liu Z 

PROVIDER: S-EPMC5688240 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature