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  Human embryonic stem cells and embryonal carcinoma cells have overlapping and distinct metabolic signatures

Abu Dawud, R., Schreiber, K., Schomburg, D., & Adjaye, J. (2012). Human embryonic stem cells and embryonal carcinoma cells have overlapping and distinct metabolic signatures. PLoS One, 7(6), e39896-e39896. doi:10.1371/journal.pone.0039896.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F01E-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F01F-9
Genre: Journal Article

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© 2012 Abu Dawud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 Creators:
Abu Dawud, Raed1, 2, Author              
Schreiber, Kerstin3, Author
Schomburg, Dietmar3, Author
Adjaye, James1, 2, Author              
Affiliations:
1Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479654              
2Stem Cell Unit, Anatomy Department, King Saud University, Riyadh, Saudi Arabia, ou_persistent22              
3Technische Universität Braunschweig, Institute for Biochemistry, Biotechnology and Bioinformatics, Braunschweig, Germany, ou_persistent22              

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Free keywords: Animals Cell Differentiation/genetics Embryonal Carcinoma Stem Cells/*metabolism Embryonic Stem Cells/*metabolism Glycolysis Green Fluorescent Proteins/metabolism Humans *Metabolome Mice Octamer Transcription Factor-3/metabolism Signal Transduction Transcriptome/genetics
 Abstract: While human embryonic stem cells (hESCs) and human embryonal carcinoma cells (hECCs) have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. Here, we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS). Whilst some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline) or lower (e.g., glutamic acid, mannitol, malic acid, GABA) in hESCs (H9) compared to hECCs (NTERA2), these represent cell type specific signatures. Further, our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O(2) while oxidative phosphorylation (OXPHOS) is impaired or even shut down. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency.

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Language(s): eng - English
 Dates: 2012-06-29
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1371/journal.pone.0039896
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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 7 (6) Sequence Number: - Start / End Page: e39896 - e39896 Identifier: ISSN: 1932-6203
CoNE: /journals/resource/1000000000277850