Journal
EMBO JOURNAL
Volume 31, Issue 9, Pages 2103-2116Publisher
WILEY
DOI: 10.1038/emboj.2012.71
Keywords
human embryonic stem cell; hypoxia-inducible factor 1 alpha; metabolism; mouse embryonic stem cell; mouse epiblast stem cell
Categories
Funding
- National Institutes of Health [DK17047, R01DK078340, P30 DK056465-11S2, R01GM083867, 1P01GM081619]
Ask authors/readers for more resources
The function of metabolic state in stemness is poorly understood. Mouse embryonic stem cells (ESC) and epiblast stem cells (EpiSC) are at distinct pluripotent states representing the inner cell mass (ICM) and epiblast embryos. Human embryonic stem cells (hESC) are similar to EpiSC stage. We now show a dramatic metabolic difference between these two stages. EpiSC/hESC are highly glycolytic, while ESC are bivalent in their energy production, dynamically switching from glycolysis to mitochondrial respiration on demand. Despite having a more developed and expanding mitochondrial content, EpiSC/hESC have low mitochondrial respiratory capacity due to low cytochrome c oxidase (COX) expression. Similarly, in vivo epiblasts suppress COX levels. These data reveal EpiSC/hESC functional similarity to the glycolytic phenotype in cancer (Warburg effect). We further show that hypoxia-inducible factor 1 alpha (HIF1 alpha) is sufficient to drive ESC to a glycolytic Activin/Nodal-dependent EpiSC-like stage. This metabolic switch during early stem-cell development may be deterministic. The EMBO Journal (2012) 31, 2103-2116. doi:10.1038/emboj.2012.71; Published online 23 March 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available