Ayako Nakamura-Ishizu
   Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Ca2+-mitochondria axis drives cell division in hematopoietic stem cells.
Journal Formal name:The Journal of experimental medicine
Abbreviation:J Exp Med
ISSN code:15409538/00221007
Domestic / ForeginForegin
Volume, Issue, Page 215(8),pp.2097-2113
Author and coauthor Umemoto Terumasa, Hashimoto Michihiro, Matsumura Takayoshi, Nakamura-Ishizu Ayako, Suda Toshio
Publication date 2018/08
Summary 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