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ID 115015
Author
Oshima, Koichi Kyoto University|Columbia University
Saiki, Norikazu Kyoto University
Tanaka, Michihiro Kyoto University
Imamura, Hiromi Kyoto University
Niwa, Akira Kyoto University
Tanimura, Ayako The University of Tokushima KAKEN Search Researchers
Nagahashi, Ayako Kyoto University
Hirayama, Akiyoshi Keio University
Okita, Keisuke Kyoto University
Hotta, Akitsu Kyoto University
Kitayama, Shuichi Kyoto University
Osawa, Mitsujiro Kyoto University
Kaneko, Shin Kyoto University
Watanabe, Akira Kyoto University
Asaka, Isao Kyoto University
Fujibuchi, Wataru Kyoto University
Imai, Kohsuke Tokyo Medical and Dental University
Yabe, Hiromasa Tokai University
Kamachi, Yoshiro Nagoya University
Hara, Junichi Osaka City General Hospital
Kojima, Seiji Nagoya University
Tomita, Masaru Keio University
Soga, Tomoyoshi Keio University
Nonoyama, Shigeaki National Defense Medical College
Nakahata, Tatsutoshi Kyoto University
Saito, Megumu K. Kyoto University
Keywords
Induced pluripotent stem cells
Adenylate kinase 2
Hemoangiogenic progenitor cells
Phosphotransfer
Content Type
Journal Article
Description
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.
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006291X
NCID
AA00564395
AA11542044
Publisher
Elsevier
Volume
497
Issue
2
Start Page
719
End Page
725
Published Date
2018-02-17
Rights
© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
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language
eng
TextVersion
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departments
Oral Sciences