Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Marsboom, G; Zhang, G-F; Pohl-Avila, N; Zhang, Y; Yuan, Y; Kang, H; Hao, B; Brunengraber, H; Malik, AB; Rehman, J

Published Date

  • July 12, 2016

Published In

Volume / Issue

  • 16 / 2

Start / End Page

  • 323 - 332

PubMed ID

  • 27346346

Pubmed Central ID

  • 27346346

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2016.05.089

Language

  • eng

Conference Location

  • United States