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Comparative Metabolomic Profiling of Rat Embryonic and Induced Pluripotent Stem Cells

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Abstract

Metabolomic profiles of somatic cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) reflect their metabolic phenotypes. The comparative study of metabolomes of these cells is important for understanding the differences in metabolism between somatic and pluripotent cells, and also the possible differences between ESCs and iPSCs. Here, we performed for the first time the metabolomic analysis of rat ESCs, iPSCs, and embryonic fibroblasts (EFs) at both quantitative and semi-quantitative levels using NMR spectroscopy and liquid chromatography with mass spectrometric detection, respectively. The total of 106 metabolites has been identified, and the concentrations of 51 compounds have been measured. It is found that the reprogramming of rat EFs into iPSCs affects virtually all metabolic pathways and causes drastic changes in the cell metabolomic profile. The difference between ESCs and iPSCs is much less pronounced: the concentrations of the majority of metabolites in ESCs and iPSCs are similar, and significant differences were observed for only several compounds, including adenosine, cysteic acid, glycerophosphoglycerol, inositol phosphate, glucose, myo-inositol, phosphoserine, xanthosine, guanosine. The observed differences between the metabolomic compositions of ESCs and iPSCs do not influence the pluripotent ability of iPSCs.

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Acknowledgements

This work was supported by the Russian Science Foundation (project № 19-75-20063).

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Suren M. Zakian conceived the experiments. All authors contributed to the study conception and design. Cells were cultured by Vladimir V. Sherstyuk. NMR and LC-MS analyzes was performed by Lyudmila V. Yanshole, Ekaterina A. Zelentsova, Arsenty D. Melnikov, Yuri P. Tsentalovich. The manuscript draft was written by Yuri P. Tsentalovich, Lyudmila V. Yanshole, and Vladimir V. Sherstyuk. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Suren M. Zakian.

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Sherstyuk, V.V., Yanshole, L.V., Zelentsova, E.A. et al. Comparative Metabolomic Profiling of Rat Embryonic and Induced Pluripotent Stem Cells. Stem Cell Rev and Rep 16, 1256–1265 (2020). https://doi.org/10.1007/s12015-020-10052-3

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