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Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells
Open accessAbstract
Relatively little is known regarding the role of mitochondrial metabolism in stem cell biology. Here we demonstrate that mouse embryonic stem cells sorted for low and high resting mitochondrial membrane potential (DeltaPsi(m)L and DeltaPsi(m)H) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, DeltaPsi(m)L cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas DeltaPsi(m)H cells behave in the opposite fashion. We further demonstrate that DeltaPsi(m) reflects the degree of overall mammalian target of rapamycin (mTOR) activation and that the mTOR inhibitor rapamycin reduces metabolic rate, augments differentiation, and inhibits tumor formation of the mouse embryonic stem cells with a high metabolic rate. Taken together, our results suggest a coupling between intrinsic metabolic parameters and stem cell fate that might form a basis for novel enrichment strategies and therapeutic options.
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Cites
Hypoxia-Inducible Factors, Stem Cells, and Cancer
Keith, B., & Simon, M. C. (2007) · Cell · doi:10.1016/j.cell.2007.04.019 · Cited by 1,179
Hypoxia requires Notch signaling to maintain the undifferentiated cell state
Gustafsson, M. V., Zheng, X., Pereira, T., Gradin, K., Jin, S., Lundkvist, J., Ruas, J. L., Poellinger, L., Lendahl, U., & Bondesson, M. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.010 · Cited by 1,109
Cited by
Stem cells and the impact of ROS signaling
Bigarella, C. L., Liang, R., & Ghaffari, S. (2014) · Development · doi:10.1242/dev.107086 · Cited by 632
Choosing between glycolysis and oxidative phosphorylation: a tumor’s dilemma?
Jose, C., Bellance, N., & Rossignol, R. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.10.012 · Cited by 518
Ramalho-Santos, J., Varum, S., Amaral, S., Mota, P. C., Sousa, A. P., & Amaral, A. (2009) · Human Reproduction Update · doi:10.1093/humupd/dmp016 · Cited by 482
Hypoxia or in situ normoxia: The stem cell paradigm
Ivanovic, Z. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21690 · Cited by 406
Schell, J. C., Olson, K. A., Jiang, L., Hawkins, A. J., Van Vranken, J. G., Xie, J., Egnatchik, R. A., Earl, E. G., DeBerardinis, R. J., & Rutter, J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.026 · Cited by 363
Metadata
- Authors
- Schieke, S. M., Ma, M., Cao, L., McCoy, J. P., Liu, C., Hensel, N. F., Barrett, A. J., Boehm, M., & Finkel, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 283
- Issue
- 42
- Pages
- 28506-28512
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2053153356
- Cited by
- 184
- References
- 2
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Schieke, S. M., Ma, M., Cao, L., McCoy, J. P., Liu, C., Hensel, N. F., Barrett, A. J., Boehm, M., & Finkel, T. (2008). Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m802763200
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