期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 497, 期 2, 页码 719-725出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.02.139
关键词
Induced pluripotent stem cells; Adenylate kinase 2; Hemoangiogenic progenitor cells; Phosphotransfer
资金
- Ministry of Health, Labour and Welfare
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) [23791169]
- Leading Project of MEXT
- Japan Society for the Promotion of Science (JSPS)
- JSPS [15J06514]
- Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics
- Core Center for iPS Cell Research of Research Center Network for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED)
- Program for Intractable Diseases Research utilizing Disease-specific iPS cells of AMED [15652070, 17935423]
- Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) of AMED [14525046]
- Practical Research Project for Rare/Intractable Diseases of AMED [17930095, 16668375]
- Research Project for Practical Applications of Regenerative Medicine from AMED
- Grants-in-Aid for Scientific Research [15K09640, 16H05194, 23791169, 15J06514, 17KT0108, 17K12900, 15K11072, 15H05581, 15K06921] Funding Source: KAKEN
AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells. (C) 2018 The Authors. Published by Elsevier Inc.
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