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Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.

Publication ,  Journal Article
Marsboom, G; Zhang, G-F; Pohl-Avila, N; Zhang, Y; Yuan, Y; Kang, H; Hao, B; Brunengraber, H; Malik, AB; Rehman, J
Published in: Cell Rep
July 12, 2016

The molecular mechanisms underlying the regulation of pluripotency by cellular metabolism in human embryonic stem cells (hESCs) are not fully understood. We found that high levels of glutamine metabolism are essential to prevent degradation of OCT4, a key transcription factor regulating hESC pluripotency. Glutamine withdrawal depletes the endogenous antioxidant glutathione (GSH), which results in the oxidation of OCT4 cysteine residues required for its DNA binding and enhanced OCT4 degradation. The emergence of the OCT4(lo) cell population following glutamine withdrawal did not result in greater propensity for cell death. Instead, glutamine withdrawal during vascular differentiation of hESCs generated cells with greater angiogenic capacity, thus indicating that modulating glutamine metabolism enhances the differentiation and functional maturation of cells. These findings demonstrate that the pluripotency transcription factor OCT4 can serve as a metabolic-redox sensor in hESCs and that metabolic cues can act in concert with growth factor signaling to orchestrate stem cell differentiation.

Duke Scholars

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

July 12, 2016

Volume

16

Issue

2

Start / End Page

323 / 332

Location

United States

Related Subject Headings

  • Reactive Oxygen Species
  • Proteolysis
  • Protein Binding
  • Octamer Transcription Factor-3
  • Neovascularization, Physiologic
  • Humans
  • Human Embryonic Stem Cells
  • Glutathione
  • Glutamine
  • Endothelial Cells
 

Citation

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ICMJE
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Marsboom, G., Zhang, G.-F., Pohl-Avila, N., Zhang, Y., Yuan, Y., Kang, H., … Rehman, J. (2016). Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4. Cell Rep, 16(2), 323–332. https://doi.org/10.1016/j.celrep.2016.05.089
Marsboom, Glenn, Guo-Fang Zhang, Nicole Pohl-Avila, Yanmin Zhang, Yang Yuan, Hojin Kang, Bo Hao, Henri Brunengraber, Asrar B. Malik, and Jalees Rehman. “Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.Cell Rep 16, no. 2 (July 12, 2016): 323–32. https://doi.org/10.1016/j.celrep.2016.05.089.
Marsboom G, Zhang G-F, Pohl-Avila N, Zhang Y, Yuan Y, Kang H, et al. Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4. Cell Rep. 2016 Jul 12;16(2):323–32.
Marsboom, Glenn, et al. “Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.Cell Rep, vol. 16, no. 2, July 2016, pp. 323–32. Pubmed, doi:10.1016/j.celrep.2016.05.089.
Marsboom G, Zhang G-F, Pohl-Avila N, Zhang Y, Yuan Y, Kang H, Hao B, Brunengraber H, Malik AB, Rehman J. Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4. Cell Rep. 2016 Jul 12;16(2):323–332.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

July 12, 2016

Volume

16

Issue

2

Start / End Page

323 / 332

Location

United States

Related Subject Headings

  • Reactive Oxygen Species
  • Proteolysis
  • Protein Binding
  • Octamer Transcription Factor-3
  • Neovascularization, Physiologic
  • Humans
  • Human Embryonic Stem Cells
  • Glutathione
  • Glutamine
  • Endothelial Cells