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Metabolic oxidation regulates embryonic stem cell differentiation

Open access
Yanes, Oscar, Clark, Julie, Wong, Diana M, Patti, Gary J, Sánchez-Ruiz, Antonio, Benton, H Paul, Trauger, Sunia A, Desponts, Caroline, Ding, Sheng, Siuzdak, Gary·2010·Nature Chemical Biology

Abstract

Metabolites offer an important unexplored complement to understanding the pluripotency of stem cells. Using mass spectrometry-based metabolomics, we show that embryonic stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. By monitoring the reduced and oxidized glutathione ratio as well as ascorbic acid levels, we demonstrate that the stem cell redox status is regulated during differentiation. Based on the oxidative biochemistry of the unsaturated metabolites, we experimentally manipulated specific pathways in embryonic stem cells while monitoring the effects on differentiation. Inhibition of the eicosanoid signaling pathway promoted pluripotency and maintained levels of unsaturated fatty acids. In contrast, downstream oxidized metabolites (e.g., neuroprotectin D1) and substrates of pro-oxidative reactions (e.g., acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells makes them particularly attuned to differentiate in response to in vivo oxidative processes such as inflammation.

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Metadata

Authors
Yanes, O., Clark, J., Wong, D. M., Patti, G. J., Sánchez-Ruiz, A., Benton, H. P., Trauger, S. A., Desponts, C., Ding, S., & Siuzdak, G.
Venue
Nature Chemical Biology
Published
2010-05-02
Volume
6
Issue
6
Pages
411-417
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
OpenAlex
W1978880986
Cited by
506
References
6
FWCI
16.42
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Metabolic oxidation regulates embryonic stem cell differentiation. https://app.cochat.ai/papers/10.1038/nchembio.364
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Yanes, O., Clark, J., Wong, D. M., Patti, G. J., Sánchez-Ruiz, A., Benton, H. P., Trauger, S. A., Desponts, C., Ding, S., & Siuzdak, G. (2010). Metabolic oxidation regulates embryonic stem cell differentiation. Nature Chemical Biology. https://doi.org/10.1038/nchembio.364

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.