Comparative Metabolomic Profiling of Rat Embryonic and Induced Pluripotent Stem Cells
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Comparative Metabolomic Profiling of Rat Embryonic and Induced Pluripotent Stem Cells Vladimir V. Sherstyuk 1 & Lyudmila V. Yanshole 1,2 & Ekaterina A. Zelentsova 2,3 & Arsenty D. Melnikov 2 & Sergey P. Medvedev 1 & Yuri P. Tsentalovich 2 & Suren M. Zakian 1 Accepted: 28 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Embryonic stem cells . Induced pluripotent stem cells . Pluripotency . Reprogramming . Rat . Metabolomics . NMR . LC-MS
Introduction Pluripotent stem cells (PSCs) are specific cells able to selfrenew and differentiate into all cell types of an adult organism. Two major types of PSCs are known – embryonic stem cells (ESCs), which are derived from the inner cell mass of the blastocyst, and induced pluripotent stem cells (iPSCs), which are reprogrammed from somatic cells by overexpression of Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12015-020-10052-3) contains supplementary material, which is available to authorized users. * Suren M. Zakian [email protected] 1
Federal Research Center Institute of Cytology and Genetics SB RAS, 10 Lavrentyeva Ave, Novosibirsk 630090, Russia
2
International Tomography Center SB RAS, Institutskaya 3a, 630090 Novosibirsk, Russia
3
Novosibirsk State University, Pirogova 2, 630090 Novosibirsk, Russia
Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) [1–3]. ESCs and iPSCs are unique models for studying early development, cell differentiation, modelling hereditary diseases and cell replacement therapy. The pluripotent state and selfrenewal of these cells are controlled by a complex regulatory network that has been compreh
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