イシズ アヤコ   Ayako Nakamura-Ishizu
  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 Ca2+-mitochondria axis drives cell division in hematopoietic stem cells.
掲載誌名 正式名:The Journal of experimental medicine
略  称:J Exp Med
ISSNコード:15409538/00221007
掲載区分国外
巻・号・頁 215(8),pp.2097-2113
著者・共著者 Umemoto Terumasa, Hashimoto Michihiro, Matsumura Takayoshi, Nakamura-Ishizu Ayako, Suda Toshio
発行年月 2018/08
概要 Most of the hematopoietic stem cells (HSCs) within the bone marrow (BM) show quiescent state with a low mitochondrial membrane potential (ΔΨm). In contrast, upon stress hematopoiesis, HSCs actively start to divide. However, the underlying mechanism for the initiation of HSC division still remains unclear. To elucidate the mechanism underlying the transition of cell cycle state in HSCs, we analyzed the change of mitochondria in HSCs after BM suppression induced by 5-fluoruracil (5-FU). We found that HSCs initiate cell division after exhibiting enhanced ΔΨm as a result of increased intracellular Ca2+ level. Although further activation of Ca2+-mitochondria pathway led to loss of HSCs after cell division, the appropriate suppression of intracellular Ca2+ level by exogenous adenosine or Nifedipine, a Ca2+ channel blocker, prolonged cell division interval in HSCs, and simultaneously achieved both cell division and HSC maintenance. Collectively, our results indicate that the Ca2+-mitochondria pathway induces HSC division critically to determine HSC cell fate.
DOI 10.1084/jem.20180421
PMID 29946000