Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4
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 pluripo...
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doaj-8f9120bb5dee4017ad7497e7a7ba2eba2020-11-25T01:17:13ZengElsevierCell Reports2211-12472016-07-0116232333210.1016/j.celrep.2016.05.089Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4Glenn Marsboom0Guo-Fang Zhang1Nicole Pohl-Avila2Yanmin Zhang3Yang Yuan4Hojin Kang5Bo Hao6Henri Brunengraber7Asrar B. Malik8Jalees Rehman9Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADivision of Endocrinology, Metabolism and Nutrition, Department of Medicine, Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USADivision of Cardiology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USADivision of Cardiology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USAThe 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 OCT4lo 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.http://www.sciencedirect.com/science/article/pii/S2211124716307021 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Glenn Marsboom Guo-Fang Zhang Nicole Pohl-Avila Yanmin Zhang Yang Yuan Hojin Kang Bo Hao Henri Brunengraber Asrar B. Malik Jalees Rehman |
spellingShingle |
Glenn Marsboom Guo-Fang Zhang Nicole Pohl-Avila Yanmin Zhang Yang Yuan Hojin Kang Bo Hao Henri Brunengraber Asrar B. Malik Jalees Rehman Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4 Cell Reports |
author_facet |
Glenn Marsboom Guo-Fang Zhang Nicole Pohl-Avila Yanmin Zhang Yang Yuan Hojin Kang Bo Hao Henri Brunengraber Asrar B. Malik Jalees Rehman |
author_sort |
Glenn Marsboom |
title |
Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4 |
title_short |
Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4 |
title_full |
Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4 |
title_fullStr |
Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4 |
title_full_unstemmed |
Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4 |
title_sort |
glutamine metabolism regulates the pluripotency transcription factor oct4 |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-07-01 |
description |
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 OCT4lo 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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716307021 |
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