TY - JOUR
T1 - Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors
AU - Oshima, Koichi
AU - Saiki, Norikazu
AU - Tanaka, Michihiro
AU - Imamura, Hiromi
AU - Niwa, Akira
AU - Tanimura, Ayako
AU - Nagahashi, Ayako
AU - Hirayama, Akiyoshi
AU - Okita, Keisuke
AU - Hotta, Akitsu
AU - Kitayama, Shuichi
AU - Osawa, Mitsujiro
AU - Kaneko, Shin
AU - Watanabe, Akira
AU - Asaka, Isao
AU - Fujibuchi, Wataru
AU - Imai, Kohsuke
AU - Yabe, Hiromasa
AU - Kamachi, Yoshiro
AU - Hara, Junichi
AU - Kojima, Seiji
AU - Tomita, Masaru
AU - Soga, Tomoyoshi
AU - Noma, Takafumi
AU - Nonoyama, Shigeaki
AU - Nakahata, Tatsutoshi
AU - Saito, Megumu K.
N1 - Funding Information:
Funding was provided by grants from the Ministry of Health, Labour and Welfare to S.N. and T.N., a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to T.N. and K.Oshima ( 23791169 ), grants from the Leading Project of MEXT to T.N., a grant from the Funding Program for World-Leading Innovative Research and Development on Science and Technology (FIRST Program) of the Japan Society for the Promotion of Science (JSPS) to T.N., a grant from JSPS for JSPS Fellows to N.S. ( 15J06514 ), grants from the JSPS to T.N. and M.K.S. and a grant from Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics to K.Oshima, the 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) to T.N. and M.K.S., the Program for Intractable Diseases Research utilizing Disease-specific iPS cells of AMED ( 15652070 to I.A., T.N. and M.K.S. and 17935423 to M.K.S.), Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) of AMED ( 14525046 ) to M.K.S., Practical Research Project for Rare/Intractable Diseases of AMED ( 17930095 and 16668375 ) to M.K.S., and Research Project for Practical Applications of Regenerative Medicine from AMED to M.K.S.
Publisher Copyright:
© 2018 The Authors
PY - 2018/3/4
Y1 - 2018/3/4
N2 - 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.
AB - 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.
KW - Adenylate kinase 2
KW - Hemoangiogenic progenitor cells
KW - Induced pluripotent stem cells
KW - Phosphotransfer
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U2 - 10.1016/j.bbrc.2018.02.139
DO - 10.1016/j.bbrc.2018.02.139
M3 - Article
C2 - 29462620
AN - SCOPUS:85042294757
SN - 0006-291X
VL - 497
SP - 719
EP - 725
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -