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

Baojiang Wu, Yunxia Li, Bojiang Li, Baojing Zhang, Yanqiu Wang, Lin Li, Junpeng Gao, Yuting Fu, Shudong Li, Chen Chen, Azim Surani, Fuchou Tang (+3 others)
Naive pluripotency can be maintained in medium with two inhibitors plus leukemia inhibitory factor (2i/LIF) supplementation, which primarily affects canonical WNT, FGF/ERK, and JAK/STAT3 signaling. However, whether one of these three supplements alone is sufficient to maintain naive self-renewal remains unclear. Here we show that LIF alone in medium is sufficient for adaptation of 2i/L-ESCs to embryonic stem cells (ESCs) in a hypermethylated state (L-ESCs). Global transcriptomic analysis shows
more » ... hat L-ESCs are close to 2i/ L-ESCs and in a stable state between naive and primed pluripotency. Notably, our results demonstrate that DNA methyltransferases (DNMTs) play an important role in LIF-dependent mouse ESC adaptation and self-renewal. LIF-dependent ESC 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 chimeras. L-ESCs cultured under such simple conditions as in this study would provide a more conducive platform to clarify the molecular mechanism of ESCs in in vitro culture. 582
doi:10.17863/cam.68344 fatcat:tjhx5rhg3vactdg7jtntxhxjom