The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells
Open accessAbstract
Summary Defining the metabolic programs that underlie stem cell maintenance will be essential for developing strategies to manipulate stem cell capacity. Mammalian hematopoietic stem cells (HSCs) maintain cell cycle quiescence in a hypoxic microenvironment. It has been proposed that HSCs exhibit a distinct metabolic phenotype under these conditions. Here we directly investigated this idea using metabolomic analysis and found that HSCs generate adenosine-5′-triphosphate by anaerobic glycolysis through a pyruvate dehydrogenase kinase (Pdk)-dependent mechanism. Elevated Pdk expression leads to active suppression of the influx of glycolytic metabolites into mitochondria. Pdk overexpression in glycolysis-defective HSCs restored glycolysis, cell cycle quiescence, and stem cell capacity, while loss of both Pdk2 and Pdk4 attenuated HSC quiescence, glycolysis, and transplantation capacity. Moreover, treatment of HSCs with a Pdk mimetic promoted their survival and transplantation capacity. Thus, glycolytic metabolic status governed by Pdk acts as a cell cycle checkpoint that modulates HSC quiescence and function.
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1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601
RetractedZhou, S., Schuetz, J. D., Bunting, K. D., Colapietro, A.-M., Sampath, J., Morris, J. J., Lagutina, I., Grosveld, G. C., Osawa, M., Nakauchi, H., et al. (2001) · Nature Medicine · doi:10.1038/nm0901-1028 · Cited by 2,280 · cited 2×
“The Side Population (SP) phenotype of LT-HSCs is marked by expression of the ATP-dependent transporter Bcrp1 (Goodell et al., 1996, 1997; Zhou et al., 2001) and maintained by intracel- lular ATP production.”
Telomere dysfunction induces metabolic and mitochondrial compromise
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Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106
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Tumor suppressors and cell metabolism: a recipe for cancer growth
Jones, R. G., & Thompson, C. B. (2009) · Genes & Development · doi:10.1101/gad.1756509 · Cited by 1,085
Metabolic Regulation of Hematopoietic Stem Cells in the Hypoxic Niche
Suda, T., Takubo, K., & Semenza, G. L. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.09.010 · Cited by 844
Self-citationLkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
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Bmi1 regulates mitochondrial function and the DNA damage response pathway
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Ito, K., & Suda, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3772 · Cited by 1,014
Self-citationPalantir characterizes cell fate continuities in human hematopoiesis
Setty, M., Kiseliovas, V., Levine, J., Gayoso, A., Mazutis, L., & Pe’er, D. (2018) · doi:10.1101/385328 · Cited by 836
Characterization of cell fate probabilities in single-cell data with Palantir
Setty, M., Kiseliovas, V., Levine, J., Gayoso, A., Mazutis, L., & Pe’er, D. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0068-4 · Cited by 833
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Metadata
- Authors
- Takubo, K., Nagamatsu, G., Kobayashi, C. I., Nakamura-Ishizu, A., Kobayashi, H., Ikeda, E., Goda, N., Rahimi, Y., Johnson, R. S., Soga, T., Hirao, A., Suematsu, M., & Suda, T.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 12
- Issue
- 1
- Pages
- 49-61
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2074516296
- Cited by
- 806
- References
- 10
- FWCI
- 35.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Takubo, K., Nagamatsu, G., Kobayashi, C. I., Nakamura-Ishizu, A., Kobayashi, H., Ikeda, E., Goda, N., Rahimi, Y., Johnson, R. S., Soga, T., Hirao, A., Suematsu, M., & Suda, T. (2013). Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells. Cell Stem Cell. https://doi.org/10.1016/j.stem.2012.10.011
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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