RNA-Seq dataset of wild type and PRC2 mutant mouse embryonic stem cells undergoing ground state conversion.

Mouse embryonic stem cells (mESCs) represent an exceptional model for understanding how transcriptional responses are regulated by signalling pathways during development. Treatment with a cocktail of MEK and GSK3β inhibitors ("2i") induces ground state pluripotency, characterized by increased self-renewal, reduced DNA methylation, and uniformly high expression of pluripotency markers. Polycomb Repressive Complex 2 (PRC2) is a key developmental regulator controlling stem cell self-renewal and differentiation decisions, and altered expression of PRC2 target genes is a signature of 2i-mediated ground state conversion. Here, we generated a comprehensive RNA sequencing dataset from mESCs subjected to 2i conversion time-course across five time points between 0 and 96 h. We analysed two independently derived wild type lines, and two isogenic Cas9-edited lines carrying loss-of-function mutations in core PRC2 subunits Enhancer of Zeste Homolog 2 (Ezh2) or Embryonic Ectoderm Development (Eed). These data provide a resource to understand the temporal patterns of transcriptional responses to MEK and GSK3β inhibitors and explore the role of PRC2 function in regulation of pluripotency circuit.