Induced Pluripotent Stem Cells Show Metabolomic Differences to Embryonic Stem Cells in Polyunsaturated Phosphatidylcholines and Primary Metabolism

University of California Davis Genome Center, University of California Davis, Davis, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 10/2012; 7(10):e46770. DOI: 10.1371/journal.pone.0046770
Source: PubMed


Induced pluripotent stem cells are different from embryonic stem cells as shown by epigenetic and genomics analyses. Depending on cell types and culture conditions, such genetic alterations can lead to different metabolic phenotypes which may impact replication rates, membrane properties and cell differentiation. We here applied a comprehensive metabolomics strategy incorporating nanoelectrospray ion trap mass spectrometry (MS), gas chromatography-time of flight MS, and hydrophilic interaction- and reversed phase-liquid chromatography-quadrupole time-of-flight MS to examine the metabolome of induced pluripotent stem cells (iPSCs) compared to parental fibroblasts as well as to reference embryonic stem cells (ESCs). With over 250 identified metabolites and a range of structurally unknown compounds, quantitative and statistical metabolome data were mapped onto a metabolite networks describing the metabolic state of iPSCs relative to other cell types. Overall iPSCs exhibited a striking shift metabolically away from parental fibroblasts and toward ESCs, suggestive of near complete metabolic reprogramming. Differences between pluripotent cell types were not observed in carbohydrate or hydroxyl acid metabolism, pentose phosphate pathway metabolites, or free fatty acids. However, significant differences between iPSCs and ESCs were evident in phosphatidylcholine and phosphatidylethanolamine lipid structures, essential and non-essential amino acids, and metabolites involved in polyamine biosynthesis. Together our findings demonstrate that during cellular reprogramming, the metabolome of fibroblasts is also reprogrammed to take on an ESC-like profile, but there are select unique differences apparent in iPSCs. The identified metabolomics signatures of iPSCs and ESCs may have important implications for functional regulation of maintenance and induction of pluripotency.

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Available from: Dinesh Barupal
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    • "Moreover, those hypothetical induced pluripotent stem cells caused more immune rejections in recipient mice than normal embryonic stem cells [15] . In comparison with normal embryonic stem cells, those so-called induced pluripotent stem cells had different metabolic activities [16] [17] . In a major turn of events, the very same laboratory that pioneered these supposed stem cells has now reported that the believed human induced pluripotent stem cells were actually different from real human embryonic stem cells in several aspects [18] . "
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    ABSTRACT: The claimed human induced pluripotent stem cells (iPSCs) are not equivalent to human embryonic or adult stem cells. These should be redefined as induced pluripotent stem cell-like cells. We do not think that those so-called induced pluripotent stem cells will be a reliable and feasible source of stem cells for the foreseeable future.
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    • "It should be noted that the putrescine content depends not only on the biosynthetic ODC activity, but also on the level of the catabolic enzyme SSAT, which is low in stem cells, but increases across differentiation, such as following 1,25-dihydroxyvitamin- D3-mediated osteogenesis (Tjabringa et al. 2008). Reduction of the putrescine content has been indeed recently reported to be pivotal in cellular reprogramming of mouse fibroblasts to induced pluripotent stem cells (Meissen et al. 2012). Actually, SSAT has been indicated as a key metabolic regulator, able not only to regulate polyamine content , but also to directly affect HIF-1, NF-jB and integrinmediated signaling (Pegg 2008). "
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    • "Using MS, Yanes et al. reported a reduction in the abundance of unsaturated metabolites (phospholipids) as ESCs undergo commitment to cardiac muscle cells and neurons (Yanes et al., 2010) conjecturing that stem cells differentiate in response to oxidative processes such as inflammation. Differences in polyunsaturated phosphatidylcholines and other metabolic compounds between mouse iPSCs and mESCs and between iPSCs and the parent fibroblasts undergoing reprogramming (Meissen et al., 2012). In addition, analysis of mESC extracts showed dependence of cell proliferation in vitro on threonine catabolism (Wang et al., 2009a). "
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