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Fatty acid oxidation is required for embryonic stem cell survival during metabolic stress

  1. Author:
    Yan, Hualong
    Malik, Navdeep
    Kim, Young-Im
    He,Yunlong
    Li, Mangmang
    Dubois, Wendy
    Liu, Huaitian
    Peat, Tyler J
    Nguyen, Joe T
    Tseng, Yu-Chou
    Ayaz, Gamze
    Alzamzami, Waseem
    Chan,King
    Andresson,Thorkell
    Tessarollo,Lino
    Mock, Beverly A
    Lee, Maxwell P
    Huang, Jing [ORCID]

  2. Author Address

    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Sequencing Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA., Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China., Cancer Research Technology Program, Protein Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA., Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.,
    1. Year: 2021
    2. Date: Jun 4
    3. Epub Date: 2021 May 05
  2. Journal: EMBO Reports
    1. 22
    2. 6
  4. Type of Article: Article
  5. Article Number: e52122
  6. ISSN: 1469-221X
  1. Abstract:

    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. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

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External Sources

  1. View Full Text
  2. DOI: 10.15252/embr.202052122
  3. PMID: 33950553
  4. PMCID: PMC8183408
  5. View record in Web of Science®
  6. WOS: 000647130400001

Library Notes

  1. Fiscal Year: FY2020-2021
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