Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors

Koichi Oshima, Norikazu Saiki, Michihiro Tanaka, Hiromi Imamura, Akira Niwa, Ayako Tanimura, Ayako Nagahashi, Akiyoshi Hirayama, Keisuke Okita, Akitsu Hotta, Shuichi Kitayama, Mitsujiro Osawa, Shin Kaneko, Akira Watanabe, Isao Asaka, Wataru Fujibuchi, Kohsuke Imai, Hiromasa Yabe, Yoshiro Kamachi, Junichi Hara & 7 others Seiji Kojima, Masaru Tomita, Tomoyoshi Soga, Takafumi Noma, Shigeaki Nonoyama, Tatsutoshi Nakahata, Megumu K. Saito

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)719-725
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume497
Issue number2
DOIs
Publication statusPublished - 2018 Mar 4

Fingerprint

Stem cells
Induced Pluripotent Stem Cells
Energy Metabolism
Stem Cells
Adenosine Triphosphate
Hematopoietic Stem Cells
Severe Combined Immunodeficiency
Mitochondria
Organelles
Neutrophils
Phosphotransferases
Electron energy levels
Mutation
Cells
Reticular dysgenesis

Keywords

  • Adenylate kinase 2
  • Hemoangiogenic progenitor cells
  • Induced pluripotent stem cells
  • Phosphotransfer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors. / Oshima, Koichi; Saiki, Norikazu; Tanaka, Michihiro; Imamura, Hiromi; Niwa, Akira; Tanimura, Ayako; Nagahashi, Ayako; Hirayama, Akiyoshi; Okita, Keisuke; Hotta, Akitsu; Kitayama, Shuichi; Osawa, Mitsujiro; Kaneko, Shin; Watanabe, Akira; Asaka, Isao; Fujibuchi, Wataru; Imai, Kohsuke; Yabe, Hiromasa; Kamachi, Yoshiro; Hara, Junichi; Kojima, Seiji; Tomita, Masaru; Soga, Tomoyoshi; Noma, Takafumi; Nonoyama, Shigeaki; Nakahata, Tatsutoshi; Saito, Megumu K.

In: Biochemical and Biophysical Research Communications, Vol. 497, No. 2, 04.03.2018, p. 719-725.

Research output: Contribution to journalArticle

Oshima, K, Saiki, N, Tanaka, M, Imamura, H, Niwa, A, Tanimura, A, Nagahashi, A, Hirayama, A, Okita, K, Hotta, A, Kitayama, S, Osawa, M, Kaneko, S, Watanabe, A, Asaka, I, Fujibuchi, W, Imai, K, Yabe, H, Kamachi, Y, Hara, J, Kojima, S, Tomita, M, Soga, T, Noma, T, Nonoyama, S, Nakahata, T & Saito, MK 2018, 'Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors', Biochemical and Biophysical Research Communications, vol. 497, no. 2, pp. 719-725. https://doi.org/10.1016/j.bbrc.2018.02.139
Oshima, Koichi ; Saiki, Norikazu ; Tanaka, Michihiro ; Imamura, Hiromi ; Niwa, Akira ; Tanimura, Ayako ; Nagahashi, Ayako ; Hirayama, Akiyoshi ; Okita, Keisuke ; Hotta, Akitsu ; Kitayama, Shuichi ; Osawa, Mitsujiro ; Kaneko, Shin ; Watanabe, Akira ; Asaka, Isao ; Fujibuchi, Wataru ; Imai, Kohsuke ; Yabe, Hiromasa ; Kamachi, Yoshiro ; Hara, Junichi ; Kojima, Seiji ; Tomita, Masaru ; Soga, Tomoyoshi ; Noma, Takafumi ; Nonoyama, Shigeaki ; Nakahata, Tatsutoshi ; Saito, Megumu K. / Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors. In: Biochemical and Biophysical Research Communications. 2018 ; Vol. 497, No. 2. pp. 719-725.
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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.

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