期刊
STEM CELL REPORTS
卷 16, 期 3, 页码 582-596出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2021.01.017
关键词
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资金
- Program of Higher-Level Talents of Inner Mongolia University
- Inner Mongolia Autonomous Region Science and Technology Plan of China [2020ZD0007]
- National Natural Science Foundation of China [31560335]
- Ministry of Science and Technology of China [2017YFA0102702]
The study demonstrates that only LIF in the medium is sufficient for adapting 2i/L-ESCs to embryonic stem cells (ESCs) in a hypermethylated state (L-ESCs). L-ESCs are close to 2i/L-ESCs and in a stable state between naive and primed pluripotency, with an important role of DNA methyltransferases (DNMTs) in LIF-dependent mouse ESC adaptation and self-renewal.
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 suffi-cient 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 that 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.
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