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Title: Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors
Authors: Oshima, Koichi
Saiki, Norikazu
Tanaka, Michihiro
Imamura, Hiromi  kyouindb  KAKEN_id  orcid (unconfirmed)
Niwa, Akira  kyouindb  KAKEN_id
Tanimura, Ayako
Nagahashi, Ayako
Hirayama, Akiyoshi
Okita, Keisuke  kyouindb  KAKEN_id  orcid (unconfirmed)
Hotta, Akitsu  kyouindb  KAKEN_id  orcid (unconfirmed)
Kitayama, Shuichi
Osawa, Mitsujiro
Kaneko, Shin
Watanabe, Akira  kyouindb  KAKEN_id  orcid (unconfirmed)
Asaka, Isao  kyouindb  KAKEN_id
Fujibuchi, Wataru  kyouindb  KAKEN_id
Imai, Kohsuke
Yabe, Hiromasa
Kamachi, Yoshiro
Hara, Junichi
Kojima, Seiji
Tomita, Masaru
Soga, Tomoyoshi
Noma, Takafumi
Nonoyama, Shigeaki
Nakahata, Tatsutoshi
Saito, Megumu K.
Author's alias: 佐伯, 憲和
田中, 道廣
今村, 博臣
丹羽, 明
沖田, 圭介
堀田, 秋津
喜多山, 秀一
大澤, 光次郎
金子, 新
渡辺, 亮
浅香, 勲
藤渕, 航
中畑, 龍俊
斎藤, 潤
Keywords: Induced pluripotent stem cells
Adenylate kinase 2
Hemoangiogenic progenitor cells
Issue Date: 4-Mar-2018
Publisher: Elsevier BV
Journal title: Biochemical and Biophysical Research Communications
Volume: 497
Issue: 2
Start page: 719
End page: 725
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.
Rights: © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (
DOI(Published Version): 10.1016/j.bbrc.2018.02.139
PubMed ID: 29462620
Appears in Collections:Journal Articles

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