Metabolic oxidation regulates embryonic stem cell differentiation
| Autor: | Gary J. Patti, Caroline Desponts, Sunia A. Trauger, Gary Siuzdak, Sheng Ding, Antonio Sánchez-Ruiz, Julie Clark, Diana M. Wong, Oscar Yanes, H. Paul Benton |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Proteome
Cellular differentiation Carboxylic Acids Oxidative phosphorylation Biology Article Metabolomics Carnitine Metabolome Humans Amino Acids Molecular Biology Embryonic Stem Cells Stem Cells Cell Differentiation Cell Biology Ascorbic acid Embryonic stem cell Glutathione Cell biology Phenotype Biochemistry Gene Expression Regulation Eicosanoids Stem cell Signal transduction Oxidation-Reduction Software |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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