HIF-2α regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth
University of Pennsylvania · Cancer Research Institute of the Slovak Academy of Sciences · +1 more institution
Abstract
The division, differentiation, and function of stem cells and multipotent progenitors are influenced by complex signals in the microenvironment, including oxygen availability. Using a genetic "knock-in" strategy, we demonstrate that targeted replacement of the oxygen-regulated transcription factor HIF-1alpha with HIF-2alpha results in expanded expression of HIF-2alpha-specific target genes including Oct-4, a transcription factor essential for maintaining stem cell pluripotency. We show that HIF-2alpha, but not HIF-1alpha, binds to the Oct-4 promoter and induces Oct-4 expression and transcriptional activity, thereby contributing to impaired development in homozygous Hif-2alpha KI/KI embryos, defective…
Citation impact
- FWCI
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- Percentile
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- References
- 67
Authors
9- KLKelly L. CovelloCorresponding
University of Pennsylvania
- JKJames Kehler
University of Pennsylvania
- HDHongwei D. Yu
Cancer Research Institute of the Slovak Academy of Sciences, University of Pennsylvania
- JDJohn D. Gordan
Cancer Research Institute of the Slovak Academy of Sciences, University of Pennsylvania
- AMAndrew M. Arsham
Cancer Research Institute of the Slovak Academy of Sciences, University of Pennsylvania
Topics & keywords
- Biology
- Embryoid body
- Embryonic stem cell
- Cell biology
- Stem cell
- Transcription factor
- Cellular differentiation
- Progenitor cell