イシズ　アヤコ   ISHIZU Ayako   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells.
掲載誌名	正式名：Cell stem cell 略　 称：Cell Stem Cell ISSNコード：18759777/18759777
掲載区分	国外
巻・号・頁	12(1),pp.49-61
著者・共著者	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
発行年月	2013/01
概要	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