A High Glycolytic Flux Supports the Proliferative Potential of Murine Embryonic Stem Cells
Abstract
Embryonic stem (ES) cells are immortal and present the ability to self-renew while retaining their ability to differentiate. In contrast, most primary cells possess a limited proliferative potential, and when this is exhausted, undergo an irreversible growth arrest termed senescence. In primary cells, senescence can be also triggered by a variety of stress to which ES cells are highly refractory. Here the authors report that the proliferative capacity of murine ES cells closely correlates with high activity of different glycolytic enzymes, elevated glycolytic flux, and low mitochondrial oxygen consumption. The direct relation between glycolytic flux and the ability of ES cells to proliferate is further remarked in experiments where glycolysis or ES cell self-renewal was specifically inhibited. It was previously reported that the upregulation of glycolysis in primary cells results in life span extension. The authors hypothesize that the naturally high glycolytic flux observed in murine ES cells can be responsible for their unlimited proliferative potential.
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These cells are resistant to a variety of stresses that induce senescence in primary cells, suggesting that some tissue stem cells do not use the senescence anti-tumor barrier in response to oncogenic insults.
“These cells are resistant to a variety of stresses that induce senescence in primary cells (23), suggesting that some tissue stem cells do not use the senescence anti-tumor barrier in response to oncogenic insults.”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [23]
A high glycolytic flux correlated with the unlimited proliferative potential that characterizes embryonic stem cells.
“A high glycolytic flux also correlated with the unlimited proliferative potential that characterizes embryonic stem cells (23).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [23]
Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · see citing works
Self-citationExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
Cellular and developmental control of O <sub>2</sub> homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476 · see citing works
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745 · see citing works
Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1
Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., & Dimri, G. P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.389-401.2003 · Cited by 438 · see citing works
McConnell, B. B., Starborg, M., Brookes, S., & Peters, G. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70137-x · Cited by 314 · see citing works
Ogryzko, V. V., Hirai, T. H., Russanova, V. R., Barbie, D. A., & Howard, B. H. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.5210 · Cited by 268 · see citing works
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Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · see citing works
Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer
Pate, K. T., Stringari, C., Sprowl‐Tanio, S., Wang, K., TeSlaa, T., Hoverter, N. P., McQuade, M. M., Garner, C., Digman, M. A., Teitell, M. A., et al. (2014) · The EMBO Journal · doi:10.15252/embj.201488598 · Cited by 459 · see citing works
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · see citing works
James, E. L., Michalek, R. D., Pitiyage, G. N., de Castro, A. M., Vignola, K. S., Jones, J., Mohney, R. P., Karoly, E. D., Prime, S. S., & Parkinson, E. K. (2015) · Journal of Proteome Research · doi:10.1021/pr501221g · Cited by 231 · see citing works
Autophagy in stem cells: repair, remodelling and metabolic reprogramming
Boya, P., Codogno, P., & Rodriguez-Muela, N. (2018) · Development · doi:10.1242/dev.146506 · Cited by 197 · see citing works
Pala, F., Di Girolamo, D., Mella, S., Yennek, S., Chatre, L., Ricchetti, M., & Tajbakhsh, S. (2018) · Journal of Cell Science · doi:10.1242/jcs.212977 · Cited by 184 · see citing works
Correlation of brain amyloid with “aerobic glycolysis”: a question of assumptions?
Phelps, M. E., & Barrio, J. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012684107 · Cited by 12 · see citing works
- Authors
- Kondoh, H., Lleonart, M. E., Nakashima, Y., Yokode, M., Tanaka, M., Bernard, D., Gil, J., & Beach, D.
- Affiliations
- Kyoto University (JP)
- Vall d'Hebron Hospital Universitari (ES)
- Kyoto University Hospital (JP)
- Centre National de la Recherche Scientifique (FR)
- Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom.
- Center for Cutaneous Biology, Institute for Cell and Molecular Science, London, United Kingdom.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2007-03
- Volume
- 9
- Issue
- 3
- Pages
- 293-299
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W1986500594
- Cited by
- 325
- References
- 7
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 14 · 2023: 10 · 2022: 19 · 2021: 19 · 2020: 19 · 2019: 15 · 2018: 20 · 2017: 32 · 2016: 16 · 2015: 32 · 2014: 21 · 2013: 30 · 2012: 20
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- embryonic stem cells, glycolytic flux, glycolytic enzymes, cell proliferation, self-renewal, cellular senescence, mitochondrial oxygen consumption, glycolysis inhibition, lifespan extension, primary cells
- MeSH terms
- Animals, Glycolysis, Mice, Inbred C57BL, Mitochondria, Oxygen Consumption, Cell Proliferation, Mice, Embryonic Stem Cells
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