DNMTs Play an Important Role in Maintaining the Pluripotency of Leukemia Inhibitory Factor Dependent Embryonic Stem Cells. DNMTs Play an Important Role in Maintaining the Pluripotency of Leukemia Inhibitory Factor Dependent Embryonic Stem Cells

Naïve pluripotency can be maintained in 2i/LIF supplements, which primarily affect canonical WNT, FGF/ERK, and JAK/STAT3 signaling. However, whether one of these tripartite supplements alone is sufficient to maintain naïve self-renewal remain unclear. Here we show that LIF alone medium is sufficient for adaptation of 2i/L-ESCs to ESCs with hypermethylated state (L-ESCs). Global transcriptomic analysis show that L-ESCs are close to 2i/L-ESCs and in a stable state between naïve and primed pluripotency. Notably, our results demonstrate that DNA methyltransferases (DNMTs) play an important role for LIF-dependent mouse ESCs adaptation and self-renew. LIF-dependent ESCs adaptation efficiency is significantly increased in serum treatment and reduced in Dnmt3a or Dnmt3l knockout ESCs. Importantly, unlike epiblast stem cells, L-ESCs contribute to somatic tissues and germ cells in chimaeras. L-ESCs cultured in such a simple conditions in this study would provide a more conducive platform to clarify the molecular mechanism of ESCs in vitro culture. Overall design: Replicate DNA methylation-seq datasets from mouse L-ESCs maintained in different stem cells culture conditions.