Abstract 14398: Gene Expression of Functionally Irreversible Glycolytic Enzymes is Upregulated in Derived Megakaryocytes Compared to Parent Induced Pluripotent Stem Cells
Introduction: Induced pluripotent stem cells (iPSC) can be sources for cells such as megakaryocytes (MK) that cannot be obtained easily from humans. Studies have shown that iPSC depend more on glycolysis for energy production than their somatic sources. Less is known about metabolic processes in cells differentiated from iPSC, and no studies exist for derived MK.
Hypothesis: MKs differ in glycolysis gene expression from parent iPSC.
Methods: We compared mRNA expression for glycolytic enzyme genes in 14 human iPSC lines paired with derived MK lines. Transcript abundance levels were determined in RNA-Seq data using the TopHat/Cufflinks software suite. Transcript data was filtered such that the interquartile range over the dataset was > 1 FPKM, and levels were transformed as log2(FPKM+1). MK:iPS expression ratios for genes encoding 11 glycolytic enzymes (Figure) were estimated using multilevel mixed model regression, wherein multiple transcripts were nested within a gene, and iPS/MK pairing was nested within individual. A significance threshold of p < 0.05/11 = 0.0045 was used.
Results: Of the 11 glycolytic genes studied, 6 were more highly expressed in MK, while 2 were more highly expressed in iPS (Figure). Transcripts for functionally irreversible enzymes (forward reaction highly favored, black arrows in Figure), including HK1, ADPGK and PFK, were expressed more in MK. LDHA was expressed more in iPS while LDHB was expressed more in MK reflecting the differentiation via the hemocytoblast pathway.
Conclusions: As compared to their parent iPSC lines, derived MK lines have upregulated levels of transcripts coding irreversible glycolytic enzymes committing glucose to glycolysis. This pattern differs from past comparisons of somatic source cells versus iPSC. Studies of a more diverse array of differentiated cell lines, as well as functional glucose utilization studies, will be necessary to determine if this pattern favoring glycolysis is specific to derived MK cells.
Author Disclosures: D. Vaidya: Consultant/Advisory Board; Modest; Consumable Science, Inc. K. Kammers: None. J. Martin: None. M.A. Taub: None. D. Hoyle: None. Y. Gao: None. L.R. Yanek: None. B.G. Kral: None. N. Faraday: None. R. Mathias: None. Z.Z. Wang: None. L. Cheng: None. D.M. Becker: None. L.C. Becker: None.
- © 2016 by American Heart Association, Inc.