Distinctive Krebs cycle remodeling in iPSC-derived neural and mesenchymal stem cells

Biochem Biophys Res Commun. 2019 Apr 9;511(3):658-664. doi: 10.1016/j.bbrc.2019.02.033. Epub 2019 Feb 27.

Abstract

Mitochondria play a vital role in proliferation and differentiation and their remodeling in the course of differentiation is related to the variable energy and metabolic needs of the cell. In this work, we show a distinctive mitochondrial remodeling in human induced pluripotent stem cells differentiated into neural or mesenchymal progenitors. While leading to upregulation of the citrate synthase-α-ketoglutarate dehydrogenase segment of the Krebs cycle and increased respiratory chain activities and respiration in the mesenchymal stem cells, the remodeling in the neural stem cells resulted in downregulation of α-ketoglutarate dehydrogenase, upregulation of isocitrate dehydrogenase 2 and the accumulation of α-ketoglutarate. The distinct, lineage-specific changes indicate an involvement of these Krebs cycle enzymes in cell differentiation.

Keywords: Differentiation; Induced pluripotent stem cells; Krebs cycle; Mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Line
  • Citric Acid Cycle*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mitochondria / metabolism*
  • Models, Biological
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*