Time-course transcriptome of wild type and PRC2 mutant mouse embryonic stem cells during 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 GSK3ß 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, representing six population doublings. 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 may provide a comprehensive resource to understand the temporal patterns of transcriptional responses to MEK and GSK3ß inhibitors and explore the role of PRC2 function in regulation of pluripotency circuit. Overall design: We generated a comprehensive RNA sequencing dataset from mESCs subjected to 2i conversion time-course across five time points, representing six population doublings. We analyzed 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).