Journal
STEM CELLS AND DEVELOPMENT
Volume 26, Issue 10, Pages 734-742Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2016.0320
Keywords
metabolism; oxidative phosphorylation; reprogramming efficiency; metabolomics
Funding
- National Research Foundation of Korea [NRF-2015R1A6A1A03032522, 2016R1D1A1B03931605]
- Global Research Development Center-Ministry of Education [NRF-2016K1A4A3914725]
- Ministry of Science, ICT and Future Planning [2015K000278]
- Agriculture, Ministry of Agriculture, Food and Rural Affairs [715003071HD120]
- National Research Foundation of Korea [2015K000278, 2016R1D1A1B03931605] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs. In this study, we characterized the metabolites of human fully reprogrammed iPSCs, partially reprogrammed iPSCs, and embryonic stem cells (ESCs). Using capillary electrophoresis time-of-flight mass spectrometry-based metabolomics, we found that 89% of analyzed metabolites were similarly expressed in fully reprogrammed iPSCs and human ESCs (hESCs), whereas partially reprogrammed iPSCs shared only 74% similarly expressed metabolites with hESCs. Metabolomic profiling analysis suggested that converting mitochondrial respiration to glycolytic flux is critical for reprogramming of somatic cells into fully reprogrammed iPSCs. This characterization of metabolic reprogramming in iPSCs may enable the development of new reprogramming parameters for enhancing the generation of fully reprogrammed human iPSCs.
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