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 HaraSeiji Kojima, Masaru Tomita, Tomoyoshi Soga, Takafumi Noma, Shigeaki Nonoyama, Tatsutoshi Nakahata, Megumu K. Saito

Research output: Contribution to journalArticle

5 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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors'. Together they form a unique fingerprint.

Cite this