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Ayako Nakamura-Ishizu
Department School of Medicine, School of Medicine Position Professor and Division head |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. |
| Journal | Formal name：Cell stem cell Abbreviation：Cell Stem Cell ISSN code：18759777/18759777 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 12(1),pp.49-61 |
| Author and coauthor | Takubo Keiyo, Nagamatsu Go, Kobayashi Chiharu I, Nakamura-Ishizu Ayako, Kobayashi Hiroshi, Ikeda Eiji, Goda Nobuhito, Rahimi Yasmeen, Johnson Randall S, Soga Tomoyoshi, Hirao Atsushi, Suematsu Makoto, Suda Toshio |
| Publication date | 2013/01 |
| 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. |
| DOI | 10.1016/j.stem.2012.10.011 |
| PMID | 23290136 |