GSE201218
DIS3 ribonuclease degrades Pou6f1 to promote mouse pre-implantation cell differentiation
Mammalian early embryonic development involves precisely regulated cell differentiation. Discovering new regulators and profiling their crosstalk have been extensively studied and remain open questions. To identify novel developmental repressors, we established the knockout mouse model of Dis3, an RNA exosome associated RNase. Homozygous Dis3 null embryos have morula-to-blastocyst transition arrest and they lack cell differentiation. By single embryo RNA-seq, we identified Pou6f1 accumulation by DIS3 depletion. Sustained POU6F1 binds and represses the transcription of Nanog and Cdx2. In addition, a broader role of POU6F1 in cell fate transition is also revealed from derived mouse embryonic stem cells. We also tested DIS3 mutations and discovered their effects in causing cell transformation. Our findings uncover a new regulatory pathway of DIS3-POU6F1 in regulating pre-implantation cell differentiation in early mammalian embryogenesis. Overall design: 1. Single embryo RNA-seq of mouse embryos derived from Dis3 hetereozygous mating, including wildtype, Dis3 heterozygotes and Dis3 null embryos at embryonic day 2.5 and 2.75. Multiple biological replicates are included. 2. ChIP-seq of derived mouse embryonic stem cells transfected with either mCherry or Pou6f1-mCherry. Each has two biological replicates.