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Metabolic switch and epithelial–mesenchymal transition cooperate to regulate pluripotency
Author(s) -
Sun Hao,
Yang Xiao,
Liang Lining,
Zhang Mengdan,
Li Yuan,
Chen Jinlong,
Wang Fuhui,
Yang Tingting,
Meng Fei,
Lai Xiaowei,
Li Changpeng,
He Jingcai,
He Meiai,
Xu Qiaoran,
Li Qian,
Lin Lilong,
Pei Duanqing,
Zheng Hui
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019102961
Subject(s) - reprogramming , epiblast , epithelial–mesenchymal transition , microbiology and biotechnology , induced pluripotent stem cell , biology , germ layer , epigenetics , glycolysis , embryonic stem cell , chemistry , transition (genetics) , gastrulation , embryo , genetics , cell , biochemistry , embryogenesis , metabolism , gene
Both metabolic switch from oxidative phosphorylation to glycolysis ( OGS ) and epithelial–mesenchymal transition ( EMT ) promote cellular reprogramming at early stages. However, their connections have not been elucidated. Here, when a chemically defined medium was used to induce early EMT during mouse reprogramming, a facilitated OGS was also observed at the same time. Additional investigations suggested that the two events formed a positive feedback loop via transcriptional activation, cooperated to upregulate epigenetic factors such as Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5, and accelerated pluripotency induction at the early stage. However, at late stages, by over‐inducing glycolysis and preventing the necessary mesenchymal–epithelial transition, the two events trapped the cells at a new pluripotency state between naïve and primed states and inhibited further reprogramming toward the naïve state. In addition, the pluripotent stem cells at the new state have high similarity to epiblasts from E4.5 and E5.5 embryos, and have distinct characteristics from the previously reported epiblast‐like or formative states. Therefore, the time‐dependent cooperation between OGS and EMT in regulating pluripotency should extend our understanding of related fields.