Multi-platform NMR Study of Pluripotent Stem Cells Unveils Complementary Metabolic Signatures towards Differentiation

• Published in: Scientific reports 2020-01, Vol.10 (1), p.1622-1622, Article 1622
• Main Authors: Elena-Herrmann, Bénédicte, Montellier, Emilie, Fages, Anne, Bruck-Haimson, Reut, Moussaieff, Arieh
• Format: Article
• Language: English
• Subjects: 631/1647; 631/45; 631/532; 631/61; Amino acids; Amino Acids - metabolism; Animals; Cell differentiation; Cell Differentiation - physiology; Cell fate; Cell Line; Cellular Biology; Choline; Energy metabolism; Epigenetics; Fatty acids; Humanities and Social Sciences; Life Sciences; Magnetic Resonance Spectroscopy - methods; Metabolic Networks and Pathways - physiology; Metabolic pathways; Metabolism; Metabolites; Metabolome - physiology; Metabolomics - methods; Mice; multidisciplinary; NIH 3T3 Cells; NMR; Nuclear magnetic resonance; Phenotypes; Pluripotency; Pluripotent Stem Cells - metabolism; Post-translation; Proton Magnetic Resonance Spectroscopy - methods; Science; Science (multidisciplinary); Stem cells; Subcellular Processes; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58377-w

Stem cells, poised to revolutionize current medicine, stand as major workhorses for monitoring changes in cell fate. Characterizing metabolic phenotypes is key to monitor in differentiating cells transcriptional and epigenetic shifts at a functional level and provides a non-genetic means to control cell specification. Expanding the arsenal of analytical tools for metabolic profiling of cell differentiation is therefore of importance. Here, we describe the metabolome of whole pluripotent stem cells (PSCs) using high‐resolution magic angle spinning (HR-MAS), a non-destructive approach for Nuclear Magnetic Resonance (NMR) analysis. The integrated 1 H NMR analysis results in detection of metabolites of various groups, including energy metabolites, amino acids, choline derivatives and short chain fatty acids. It unveils new metabolites that discriminate PSCs from differentiated counterparts and directly measures substrates and co-factors of histone modifying enzymes, suggesting that NMR stands as a strategic technique for deciphering metabolic regulations of histone post-translational modifications. HR-MAS NMR analysis of whole PSCs complements the much used solution NMR of cell extracts. Altogether, our multi-platform NMR investigation provides a consolidated picture of PSC metabolic signatures and of metabolic pathways involved in differentiation.