Physiological oxygen culture reveals retention of metabolic memory in human induced pluripotent stem cells

Alexandra J. Harvey, Carmel O'Brien, Jack Lambshead, John R. Sheedy, Joy Rathjen, Andrew L. Laslett, David K. Gardner

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming. When challenged with reduced oxygen concentration, ES cells have been shown to modulate carbohydrate use in a predictably way. In the same model, 2 of 3 iPS cell lines failed to regulate carbohydrate metabolism. Oxygen is a wellcharacterized regulator of cell function and embryo viability, and an inability of iPS cells to modulate metabolism in response to oxygen may indicate poor metabolic fidelity. As metabolism is linked to the regulation of the epigenome, assessment of metabolic responses of iPS cells to physiological stimuli during characterization is warranted to ensure complete cell reprogramming and as a measure of cell quality.

Original languageEnglish
Article numbere0193949
Number of pages19
JournalPLoS ONE
Volume13
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • induced pluripotent stem cells
  • oxygen
  • cell metabolism
  • oxygen metabolism
  • glucose metabolism
  • carbohydrate metabolism
  • pluripotency
  • amino acid metabolism

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