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Fatty acid oxidation is required for embryonic stem cell survival during metabolic stress
Author(s) -
Yan Hualong,
Malik Navdeep,
Kim YoungIm,
He Yunlong,
Li Mangmang,
Dubois Wendy,
Liu Huaitian,
Peat Tyler J,
Nguyen Joe T,
Tseng YuChou,
Ayaz Gamze,
Alzamzami Waseem,
Chan King,
Andresson Thorkell,
Tessarollo Lino,
Mock Beverly A,
Lee Maxwell P,
Huang Jing
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202052122
Subject(s) - embryonic stem cell , microbiology and biotechnology , stem cell , fatty acid , biology , beta oxidation , cell , biochemistry , chemistry , gene
Metabolic regulation is critical for the maintenance of pluripotency and the survival of embryonic stem cells (ESCs). The transcription factor Tfcp2l1 has emerged as a key factor for the naïve pluripotency of ESCs. Here, we report an unexpected role of Tfcp2l1 in metabolic regulation in ESCs—promoting the survival of ESCs through regulating fatty acid oxidation (FAO) under metabolic stress. Tfcp2l1 directly activates many metabolic genes in ESCs. Deletion of Tfcp2l1 leads to an FAO defect associated with upregulation of glucose uptake, the TCA cycle, and glutamine catabolism. Mechanistically, Tfcp2l1 activates FAO by inducing Cpt1a, a rate‐limiting enzyme transporting free fatty acids into the mitochondria. ESCs with defective FAO are sensitive to cell death induced by glycolysis inhibition and glutamine deprivation. Moreover, the Tfcp2l1‐Cpt1a‐FAO axis promotes the survival of quiescent ESCs and diapause‐like blastocysts induced by mTOR inhibition. Thus, our results reveal how ESCs orchestrate pluripotent and metabolic programs to ensure their survival in response to metabolic stress.