Updated on 2024/10/01

Information

 

写真a

 
ARAI FUMIO
 
Organization
Faculty of Medical Sciences Department of Stem Cell Biology and Medicine Professor
School of Medicine Department of Medicine(Joint Appointment)
Graduate School of Medical Sciences Department of Medicine(Joint Appointment)
Graduate School of Medical Sciences Department of Health Care Administration and Management(Joint Appointment)
Title
Professor
External link

Research Areas

  • Life Science / Hematology and medical oncology

Degree

  • D.D.S.

  • Ph.D.

Research History

  • なし

    なし

  • 慶應義塾大学 (専任講師)

Research Interests・Research Keywords

  • Research theme:Functional regulation of the hematopoietic niche

    Keyword:Mesenchymal stem cell

    Research period: 2023.4

  • Research theme:Regulation of stem cell aging

    Keyword:Shelterin

    Research period: 2014.4

  • Research theme:Elucidation of the molecular mechanism of asymmetric cell division of hematopoietic stem cells

    Keyword:Asymmetric cell division

    Research period: 2014.4

  • Research theme:Elucidation of the molecular mechanism that regulates the self-renewal activity of hematopoietic stem cells

    Keyword:hematopoietic stem cells, niche, asymmetric/symmetric cell divisions

    Research period: 2011.4 - 2017.3

Papers

  • POT1a deficiency in mesenchymal niches perturbs B-lymphopoiesis. International journal

    Kentaro Nakashima, Yuya Kunisaki, Kentaro Hosokawa, Kazuhito Gotoh, Hisayuki Yao, Ryosuke Yuta, Yuichiro Semba, Jumpei Nogami, Yoshikane Kikushige, Patrick S Stumpf, Ben D MacArthur, Dongchon Kang, Koichi Akashi, Shouichi Ohga, Fumio Arai

    Communications biology   6 ( 1 )   996 - 996   2023.9   eISSN:2399-3642

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Protection of telomeres 1a (POT1a) is a telomere binding protein. A decrease of POT1a is related to myeloid-skewed haematopoiesis with ageing, suggesting that protection of telomeres is essential to sustain multi-potency. Since mesenchymal stem cells (MSCs) are a constituent of the hematopoietic niche in bone marrow, their dysfunction is associated with haematopoietic failure. However, the importance of telomere protection in MSCs has yet to be elucidated. Here, we show that genetic deletion of POT1a in MSCs leads to intracellular accumulation of fatty acids and excessive ROS and DNA damage, resulting in impaired osteogenic-differentiation. Furthermore, MSC-specific POT1a deficient mice exhibited skeletal retardation due to reduction of IL-7 producing bone lining osteoblasts. Single-cell gene expression profiling of bone marrow from POT1a deficient mice revealed that B-lymphopoiesis was selectively impaired. These results demonstrate that bone marrow microenvironments composed of POT1a deficient MSCs fail to support B-lymphopoiesis, which may underpin age-related myeloid-bias in haematopoiesis.

    DOI: 10.1038/s42003-023-05374-0

    Web of Science

    Scopus

    PubMed

    researchmap

  • Loss of endothelial membrane KIT Ligand affects systemic KIT ligand levels but not bone marrow hematopoietic stem cells. International journal

    Sahoko Matsuoka, Raffaella Facchini, Tiago C Luis, Joana Carrelha, Petter S Woll, Takuo Mizukami, Bishan Wu, Hanane Boukarabila, Mario Buono, Ruggiero Norfo, Fumio Arai, Toshio Suda, Adam Mead, Claus Nerlov, Sten Eirik W Jacobsen

    Blood   142 ( 19 )   1622 - 1632   2023.8   ISSN:0006-4971 eISSN:1528-0020

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    A critical regulatory role of hematopoietic stem cell vascular niches in the bone marrow has been implicated to occur through endothelial niche cell expression of KIT Ligand. However, endothelial-derived KIT Ligand is expressed in both a soluble and membrane-bound form, and not unique to bone marrow niches and is also systemically distributed through the circulatory system. Here we confirm that upon deletion of both the soluble and membrane-bound form of endothelial-derived KIT Ligand hematopoietic stem cells are reduced in mouse bone marrow. However, deletion of endothelial-derived KIT Ligand was also accompanied by reduced soluble KIT Ligand levels in blood, precluding any conclusion as to whether the reduction in HSC numbers reflect reduced endothelial expression of KIT Ligand within HSC niches, elsewhere in the bone marrow and/or systemic sKIT Ligand produced by endothelial cells outside of the bone marrow. Notably, endothelial deletion specifically of the membrane bound form of KIT Ligand also reduced systemic levels of soluble KIT Ligand although with no effect on stem cell numbers, implicating a hematopoietic stem cell regulatory role primarily of soluble rather than membrane KIT Ligand expression in endothelial cells. In support of a role of systemic rather than local niche expression of soluble KIT Ligand, hematopoietic stem cells were unaffected in bones with deletion of KIT ligand when implanted in mice with normal systemic levels of soluble KIT Ligand. Our findings highlight the need for more specific tools to unravel niche-specific roles of regulatory cues expressed in hematopoietic niche cells in the bone marrow.

    DOI: 10.1182/blood.2022019018

    Web of Science

    Scopus

    PubMed

    researchmap

  • Modeling Stem Cell Fates using Non-Markov Processes. Reviewed International journal

    Patrick S Stumpf, Fumio Arai, Ben D MacArthur

    Cell stem cell   28 ( 2 )   187 - 190   2021.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2021.01.009

  • Transfer learning efficiently maps bone marrow cell types from mouse to human using single-cell RNA sequencing. Reviewed International journal

    Patrick S Stumpf, Xin Du, Haruka Imanishi, Yuya Kunisaki, Yuichiro Semba, Timothy Noble, Rosanna C G Smith, Matthew Rose-Zerili, Jonathan J West, Richard O C Oreffo, Katayoun Farrahi, Mahesan Niranjan, Koichi Akashi, Fumio Arai, Ben D MacArthur

    Communications biology   3 ( 1 )   736 - 736   2020.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s42003-020-01463-6

  • Machine Learning of Hematopoietic Stem Cell Divisions from Paired Daughter Cell Expression Profiles Reveals Effects of Aging on Self-Renewal. Reviewed International journal

    Fumio Arai, Patrick S Stumpf, Yoshiko M Ikushima, Kentaro Hosokawa, Aline Roch, Matthias P Lutolf, Toshio Suda, Ben D MacArthur

    Cell systems   11 ( 6 )   640 - 652   2020.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.cels.2020.11.004

  • The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. Reviewed International journal

    Kentaro Hosokawa, Ben D. MacArthur, Yoshiko Matsumoto Ikushima, Hirofumi Toyama, Yoshikazu Masuhiro, Shigemasa Hanazawa, Toshio Suda, Fumio Arai

    Nature Communications   8 ( 1 )   2017.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-017-00935-4

  • Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance Reviewed

    Science   354 ( 6316 )   1156 - 1160   2016.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/science.aaf5530

  • Prostaglandin E2 regulates murine hematopoietic stem/progenitor cells directly via EP4 receptor and indirectly through mesenchymal progenitor cells International journal

    Yoshiko Matsumoto Ikushima, Fumio Arai, Kentaro Hosokawa, Hirofumi Toyama, Keiyo Takubo, Tomoyuki Furuyashiki, Shuh Narumiya, Toshio Suda

    Blood   121 ( 11 )   1995 - 2007   2013.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2012-06-437889

  • Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells Reviewed

    Yuka Nakamura, Fumio Arai, Hiroko Iwasaki, Kentaro Hosokawa, Isao Kobayashi, Yumiko Gomei, Yoshiko Matsumoto, Hiroki Yoshihara, Toshio Suda

    Blood   116 ( 9 )   1422 - 1432   2010.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2009-08-239194

  • Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells Reviewed

    Kentaro Hosokawa, Fumio Arai, Hiroki Yoshihara, Hiroko Iwasaki, Yuka Nakamura, Yumiko Gomei, Toshio Suda

    Blood   116 ( 4 )   554 - 563   2010.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2009-05-224857

  • Cadherin-Based Adhesion Is a Potential Target for Niche Manipulation to Protect Hematopoietic Stem Cells in Adult Bone Marrow Reviewed

    Kentaro Hosokawa, Fumio Arai, Hiroki Yoshihara, Hiroko Iwasaki, Mark Hembree, Tong Yin, Yuka Nakamura, Yumiko Gomei, Keiyo Takubo, Haruko Shiama, Sahoko Matsuoka, Linheng Li, Toshio Suda

    Cell stem cell   6 ( 3 )   194 - 198   2010.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2009.04.013

  • Thrombopoietin/MPL Signaling Regulates Hematopoietic Stem Cell Quiescence and Interaction with the Osteoblastic Niche Reviewed

    Hiroki Yoshihara, Fumio Arai, Kentaro Hosokawa, Tetsuya Hagiwara, Keiyo Takubo, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Sahoko Matsuoka, Kana Miyamoto, Hiroshi Miyazaki, Takao Takahashi, Toshio Suda

    Cell stem cell   1 ( 6 )   685 - 697   2007.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2007.10.020

  • Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche Reviewed

    Fumio Arai, Atsushi Hirao, Masako Ohmura, Hidetaka Sato, Sahoko Matsuoka, Keiyo Takubo, Keisuke Ito, Gou Young Koh, Toshio Suda

    Cell   118 ( 2 )   149 - 161   2004.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.cell.2004.07.004

  • MBTD1 preserves adult hematopoietic stem cell pool size and function. International journal

    Keiyo Takubo, Phyo Wai Htun, Takeshi Ueda, Yasuyuki Sera, Masayuki Iwasaki, Miho Koizumi, Kohei Shiroshita, Hiroshi Kobayashi, Miho Haraguchi, Shintaro Watanuki, Zen-Ichiro Honda, Norimasa Yamasaki, Ayako Nakamura-Ishizu, Fumio Arai, Noboru Motoyama, Tomohisa Hatta, Tohru Natsume, Toshio Suda, Hiroaki Honda

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 32 )   e2206860120   2023.8   ISSN:0027-8424 eISSN:1091-6490

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Mbtd1 (mbt domain containing 1) encodes a nuclear protein containing a zinc finger domain and four malignant brain tumor (MBT) repeats. We previously generated Mbtd1-deficient mice and found that MBTD1 is highly expressed in fetal hematopoietic stem cells (HSCs) and sustains the number and function of fetal HSCs. However, since Mbtd1-deficient mice die soon after birth possibly due to skeletal abnormalities, its role in adult hematopoiesis remains unclear. To address this issue, we generated Mbtd1 conditional knockout mice and analyzed adult hematopoietic tissues deficient in Mbtd1. We observed that the numbers of HSCs and progenitors increased and Mbtd1-deficient HSCs exhibited hyperactive cell cycle, resulting in a defective response to exogenous stresses. Mechanistically, we found that MBTD1 directly binds to the promoter region of FoxO3a, encoding a forkhead protein essential for HSC quiescence, and interacts with components of TIP60 chromatin remodeling complex and other proteins involved in HSC and other stem cell functions. Restoration of FOXO3a activity in Mbtd1-deficient HSCs in vivo rescued cell cycle and pool size abnormalities. These findings indicate that MBTD1 is a critical regulator for HSC pool size and function, mainly through the maintenance of cell cycle quiescence by FOXO3a.

    DOI: 10.1073/pnas.2206860120

    Web of Science

    PubMed

    researchmap

  • Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis. International journal

    Yaeko Nakajima-Takagi, Motohiko Oshima, Junichiro Takano, Shuhei Koide, Naoki Itokawa, Shun Uemura, Masayuki Yamashita, Shohei Andoh, Kazumasa Aoyama, Yusuke Isshiki, Daisuke Shinoda, Atsunori Saraya, Fumio Arai, Kiyoshi Yamaguchi, Yoichi Furukawa, Haruhiko Koseki, Tomokatsu Ikawa, Atsushi Iwama

    eLife   12   2023.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBPa-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and β-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation.

    DOI: 10.7554/eLife.83004

    Scopus

    PubMed

    researchmap

  • Generation of functional oocytes from male mice in vitro. International journal

    Kenta Murakami, Nobuhiko Hamazaki, Norio Hamada, Go Nagamatsu, Ikuhiro Okamoto, Hiroshi Ohta, Yoshiaki Nosaka, Yukiko Ishikura, Tomoya S Kitajima, Yuichiro Semba, Yuya Kunisaki, Fumio Arai, Koichi Akashi, Mitinori Saitou, Kiyoko Kato, Katsuhiko Hayashi

    Nature   615 ( 7954 )   900 - 906   2023.3   ISSN:0028-0836 eISSN:1476-4687

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes1-5. Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction.

    DOI: 10.1038/s41586-023-05834-x

    Web of Science

    Scopus

    PubMed

    researchmap

  • POT1a IS ESSENTIAL FOR MESENCHYMAL NICHES SUPPORTING B CELL DEVELOPMENT

    Nakashima, K; Kunisaki, Y; Hosokawa, K; Yao, H; Yuta, R; Akashi, K; Ohga, S; Arai, F

    PEDIATRIC BLOOD & CANCER   69   2022.11   ISSN:1545-5009 eISSN:1545-5017

     More details

  • MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis. Reviewed International journal

    Yasutaka Hayashi, Kimihito C Kawabata, Yosuke Tanaka, Yasufumi Uehara, Yo Mabuchi, Koichi Murakami, Akira Nishiyama, Shigeru Kiryu, Yusuke Yoshioka, Yasunori Ota, Tatsuki Sugiyama, Keiko Mikami, Moe Tamura, Tsuyoshi Fukushima, Shuhei Asada, Reina Takeda, Yuya Kunisaki, Tomofusa Fukuyama, Kazuaki Yokoyama, Tomoyuki Uchida, Masao Hagihara, Nobuhiro Ohno, Kensuke Usuki, Arinobu Tojo, Yoshio Katayama, Susumu Goyama, Fumio Arai, Tomohiko Tamura, Takashi Nagasawa, Takahiro Ochiya, Daichi Inoue, Toshio Kitamura

    Cell reports   39 ( 6 )   110805 - 110805   2022.5   ISSN:2211-1247

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis and frequent progression to leukemia. It has long remained unresolved how MDS cells, which are less proliferative, inhibit normal hematopoiesis and eventually dominate the bone marrow space. Despite several studies implicating mesenchymal stromal or stem cells (MSCs), a principal component of the HSC niche, in the inhibition of normal hematopoiesis, the molecular mechanisms underlying this process remain unclear. Here, we demonstrate that both human and mouse MDS cells perturb bone metabolism by suppressing the osteolineage differentiation of MSCs, which impairs the ability of MSCs to support normal HSCs. Enforced MSC differentiation rescues the suppressed normal hematopoiesis in both in vivo and in vitro MDS models. Intriguingly, the suppression effect is reversible and mediated by extracellular vesicles (EVs) derived from MDS cells. These findings shed light on the novel MDS EV-MSC axis in ineffective hematopoiesis.

    DOI: 10.1016/j.celrep.2022.110805

    Web of Science

    Scopus

    PubMed

    researchmap

  • Hematopoietic Cell Isolation by Antibody-Free Flow Cytometry in the Zebrafish Embryo Reviewed

    Katsuhiro Konno, Jingjing Kobayashi-Sun, Fumio Arai, Isao Kobayashi, Daisuke Sugiyama

    Methods in molecular biology   2520   171 - 180   2022.5   ISSN:1064-3745 ISBN:9781071624364, 9781071624371 eISSN:1940-6029

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer US  

    DOI: 10.1007/7651_2021_459

    Scopus

    PubMed

    researchmap

  • A novel method to purify neutrophils enables functional analysis of zebrafish hematopoiesis. Reviewed International journal

    Katsuhiro Konno, Kasem Kulkeaw, Manabu Sasada, Takenobu Nii, Ayako Kaneyuki, Tohru Ishitani, Fumio Arai, Daisuke Sugiyama

    Genes to cells : devoted to molecular & cellular mechanisms   25 ( 12 )   770 - 781   2020.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.12810

  • Heterogeneity and 'memory' in stem cell populations. Reviewed International journal

    Patrick S Stumpf, Fumio Arai, Ben D MacArthur

    Physical biology   17 ( 6 )   065013 - 065013   2020.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1088/1478-3975/abba85

  • Impaired Osteoblastic Differentiation of MSCs Suppresses Normal Hematopoiesis in MDS

    Yasutaka Hayashi, Kimihito Cojin Kawabata, Yosuke Tanaka, Yasufumi Uehara, Shigeru Kiryu, Yasunori Ota, Yusuke Yoshioka, Yo Mabuchi, Tatsuki Sugiyama, Keiko Mikami, Moe Tamura, Tsuyoshi Fukushima, Shuhei Asada, Reina Takeda, Yuya Kunisaki, Tomofusa Fukuyama, Susumu Goyama, Kazuaki Yokoyama, Arinobu Tojo, Yoshio Katayama, Fumio Arai, Takashi Nagasawa, Takahiro Ochiya, Daichi Inoue

    BLOOD   136   2020.11

     More details

    Language:English   Publishing type:Research paper (other academic)  

    DOI: 10.1182/blood-2020-142284

  • Mitochondrial Protein Synthesis Is Essential for Terminal Differentiation of CD45- TER119-Erythroid and Lymphoid Progenitors. Reviewed International journal

    Kazuhito Gotoh, Yuya Kunisaki, Soichi Mizuguchi, Daiki Setoyama, Kentaro Hosokawa, Hisayuki Yao, Yuya Nakashima, Mikako Yagi, Takeshi Uchiumi, Yuichiro Semba, Jumpei Nogami, Koichi Akashi, Fumio Arai, Dongchon Kang

    iScience   23 ( 11 )   101654 - 101654   2020.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.isci.2020.101654

  • Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis Reviewed

    Hiroyasu Kidoya, Fumitaka Muramatsu, Teppei Shimamura, Weizhen Jia, Takashi Satoh, Yumiko Hayashi, Hisamichi Naito, Yuya Kunisaki, Fumio Arai, Masahide Seki, Yutaka Suzuki, Tsuyoshi Osawa, Shizuo Akira, Nobuyuki Takakura

    Nature communications   10 ( 1 )   2019.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-019-09028-w

  • 概日リズム制御分子を標的とした新規白血病治療薬の開発

    國崎 祐哉, 後藤 和人, 廣田 毅, 康 東天, 新井 文用

    臨床病理   67 ( 補冊 )   149 - 149   2019.10

     More details

    Language:Japanese  

  • Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo Reviewed

    Hiroshi Kobayashi, Takayuki Morikawa, Ayumi Okinaga, Fumie Hamano, Tomomi Hashidate-Yoshida, Shintaro Watanuki, Daisuke Hishikawa, Hideo Shindou, Fumio Arai, Yasuaki Kabe, Makoto Suematsu, Takao Shimizu, Keiyo Takubo

    Cell Reports   28 ( 1 )   145 - 158.e9   2019.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.celrep.2019.06.008

  • Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth Reviewed

    Tsuyoshi Oshima, Yoshimi Niwa, Keiko Kuwata, Ashutosh Srivastava, Tomoko Hyoda, Yoshiki Tsuchiya, Megumi Kumagai, Masato Tsuyuguchi, Teruya Tamaru, Akiko Sugiyama, Natsuko Ono, Norjin Zolboot, Yoshiki Aikawa, Shunsuke Oishi, Atsushi Nonami, Fumio Arai, Shinya Hagihara, Junichiro Yamaguchi, Florence Tama, Yuya Kunisaki, Kazuhiro Yagita, Masaaki Ikeda, Takayoshi Kinoshita, Steve A. Kay, Kenichiro Itami, Tsuyoshi Hirota

    Science Advances   5 ( 1 )   eaau9060 - eaau9060   2019.1

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/sciadv.aau9060

  • The role of telomere binding molecules for normal and abnormal hematopoiesis Reviewed

    Kentaro Hosokawa, Fumio Arai

    International Journal of Hematology   107 ( 6 )   646 - 655   2018.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-018-2432-4

  • Guest editorial Regulatory signaling in normal and abnormal hematopoiesis Reviewed

    Fumio Arai

    International Journal of Hematology   1 - 3   2018.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12185-018-2460-0

  • Spred1 Safeguards Hematopoietic Homeostasis against Diet-Induced Systemic Stress Reviewed

    Yuko Tadokoro, Takayuki Hoshii, Satoshi Yamazaki, Koji Eto, Hideo Ema, Masahiko Kobayashi, Masaya Ueno, Kumiko Ohta, Yuriko Arai, Eiji Hara, Kenichi Harada, Masanobu Oshima, Hiroko Oshima, Fumio Arai, Akihiko Yoshimura, Hiromitsu Nakauchi, Atsushi Hirao

    Cell Stem Cell   22 ( 5 )   713 - 725.e8   2018.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2018.04.002

  • Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS Reviewed International journal

    Takuji Yamauchi, Takeshi Masuda, Matthew C. Canver, Michael Seiler, Yuichiro Semba, Mohammad Shboul, Mohammed Al-Raqad, Manami Maeda, Vivien A.C. Schoonenberg, Mitchel A. Cole, Claudio Macias-Trevino, Yuichi Ishikawa, Qiuming Yao, Michitaka Nakano, Fumio Arai, Stuart H. Orkin, Bruno Reversade, Silvia Buonamici, Luca Pinello, Koichi Akashi, Daniel E. Bauer, Takahiro Maeda

    Cancer Cell   33 ( 3 )   386 - 400.e5   2018.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ccell.2018.01.012

  • Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression Reviewed

    Mohamed A.E. Ali, Kyoko Fuse, Yuko Tadokoro, Takayuki Hoshii, Masaya Ueno, Masahiko Kobayashi, Naho Nomura, Ha Thi Vu, Hui Peng, Ahmed M. Hegazy, Masayoshi Masuko, Hirohito Sone, Fumio Arai, Atsushi Tajima, Atsushi Hirao

    Scientific Reports   7 ( 1 )   2017.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-017-11909-3

  • Stem Cell Differentiation as a Non-Markov Stochastic Process Reviewed

    Cell Systems   5 ( 3 )   268 - 282.e7   2017.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.cels.2017.08.009

  • 造血幹細胞の自己複製・分化制御 Reviewed

    新井文用

    臨床血液   57 ( 10 )   2016.10

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

  • Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of nonhematopoietic genes Reviewed

    Shuhei Koide, Motohiko Oshima, Keiyo Takubo, Satoshi Yamazaki, Eriko Nitta, Atsunori Saraya, Kazumasa Aoyama, Yuko Kato, Satoru Miyagi, Yaeko Nakajima-Takagi, Tetsuhiro Chiba, Hirotaka Matsui, Fumio Arai, Yutaka Suzuki, Hiroshi Kimura, Hiromitsu Nakauchi, Toshio Suda, Yoichi Shinkai, Atsushi Iwama

    Blood   128 ( 5 )   638 - 649   2016.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2016-01-694810

  • Determining c-Myb protein levels can isolate functional hematopoietic stem cell subtypes Reviewed

    Hiroshi Sakamoto, Naoki Takeda, Fumio Arai, Kentaro Hosokawa, Paloma Garcia, Toshio Suda, Jon Frampton, Minetaro Ogawa

    Stem Cells   33 ( 2 )   479 - 490   2015.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/stem.1855

  • Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells Reviewed

    Masayuki Yamashita, Eriko Nitta, Go Nagamatsu, Yoshiko Matsumoto Ikushima, Kentaro Hosokawa, Fumio Arai, Toshio Suda

    Biochemical and Biophysical Research Communications   441 ( 1 )   196 - 201   2013.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2013.10.032

  • OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets Reviewed

    Yumiko Matsubara, Yukako Ono, Hidenori Suzuki, Fumio Arai, Toshio Suda, Mitsuru Murata, Yasuo Ikeda

    PLoS One   8 ( 3 )   2013.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pone.0058123

  • Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term repopulation ability of hematopoietic stem cells Reviewed

    Yoshiko Matsumoto Ikushima, Fumio Arai, Yuka Nakamura, Kentaro Hosokawa, Yoshiaki Kubota, Masanori Hirashima, Hirofumi Toyama, Toshio Suda

    Biochemical and Biophysical Research Communications   430 ( 1 )   20 - 25   2013.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2012.11.002

  • N-cadherin+ HSCs in fetal liver exhibit higher long-term bone marrow reconstitution activity than N-cadherin- HSCs Reviewed

    Hirofumi Toyama, Fumio Arai, Kentaro Hosokawa, Yoshiko Matsumoto Ikushima, Toshio Suda

    Biochemical and Biophysical Research Communications   428 ( 3 )   354 - 359   2012.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2012.10.058

  • A PML-PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance Reviewed

    18 ( 9 )   1350 - 1358   2012.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Stem-cell function is an exquisitely regulated process. Thus far, the contribution of metabolic cues to stem-cell function has not been well understood. Here we identify a previously unknown promyelocytic leukemia (PML)-peroxisome proliferator-activated receptor δ (PPAR-δ)-fatty- acid oxidation (FAO) pathway for the maintenance of hematopoietic stem cells (HSCs). We have found that loss of PPAR-δ or inhibition of mitochondrial FAO induces loss of HSC maintenance, whereas treatment with PPAR-δ agonists improved HSC maintenance. PML exerts its essential role in HSC maintenance through regulation of PPAR signaling and FAO. Mechanistically, the PML-PPAR-δ-FAO pathway controls the asymmetric division of HSCs. Deletion of Ppard or Pml as well as inhibition of FAO results in the symmetric commitment of HSC daughter cells, whereas PPAR-δ activation increased asymmetric cell division. Thus, our findings identify a metabolic switch for the control of HSC cell fate with potential therapeutic implications.

    DOI: 10.1038/nm.2882

  • Role of N-cadherin in the regulation of hematopoietic stem cells in the bone marrow niche

    Fumio Arai, Kentaro Hosokawa, Hirofumi Toyama, Yoshiko Matsumoto, Toshio Suda

    Annals of the New York Academy of Sciences   1266 ( 1 )   72 - 77   2012.8

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1749-6632.2012.06576.x

  • Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche Reviewed

    Ryohichi Sugimura, Xi C. He, Aparna Venkatraman, Fumio Arai, Andrew Box, Craig Semerad, Jeffrey S. Haug, Lai Peng, Xiao Bo Zhong, Toshio Suda, Linheng Li

    Cell   150 ( 2 )   351 - 365   2012.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.cell.2012.05.041

  • Gene expression profiling and regulatory networks in single cells

    Fumio Arai, Kentaro Hosokawa, Yoshiko Matsumoto, Hirofumi Toyama, Toshio Suda

    New Frontiers of Network Analysis in Systems Biology   1 - 13   2012.2

     More details

    Language:English  

    DOI: 10.1007/978-94-007-4330-4_1

  • Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation Reviewed

    Blood   118 ( 13 )   3613 - 3621   2011.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2010-06-289207

  • Telomerase reverse transcriptase protectsATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism Reviewed

    Eriko Nitta, Masayuki Yamashita, Kentaro Hosokawa, Ming Ji Xian, Keiyo Takubo, Fumio Arai, Shinichiro Nakada, Toshio Suda

    Blood   117 ( 16 )   4169 - 4180   2011.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2010-08-297390

  • Acquisition of G0 state by CD34-positive cord blood cells after bone marrow transplantation Reviewed

    Haruko Shima, Keiyo Takubo, Naoko Tago, Hiroko Iwasaki, Fumio Arai, Takao Takahashi, Toshio Suda

    Experimental Hematology   38 ( 12 )   1231 - 1240   2010.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.exphem.2010.08.004

  • TIMP-3 recruits quiescent hematopoietic stem cells into active cell cycle and expands multipotent progenitor pool Reviewed

    Hideaki Nakajima, Miyuki Ito, David S. Smookler, Fumi Shibata, Yumi Fukuchi, Yoshihiro Morikawa, Yuichi Ikeda, Fumio Arai, Toshio Suda, Rama Khokha, Toshio Kitamura

    Blood   116 ( 22 )   4474 - 4482   2010.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2010-01-266528

  • Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver Reviewed

    Hiroko Iwasaki, Fumio Arai, Yoshiaki Kubota, Maria Dahl, Toshio Suda

    Blood   116 ( 4 )   544 - 553   2010.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood-2009-08-240903

  • Erratum Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells (Nature Medicine (2006)12 (446-451)) Reviewed

    Keisuke Ito, Atsushi Hirao, Fumio Arai, Keiyo Takubo, Sahoko Matsuoka, Kana Miyamoto, Masako Ohmura, Kazuhito Naka, Kentaro Hosokawa, Yasuo Ikeda, Toshio Suda

    Nature medicine   16 ( 1 )   2010.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm0110-129a

  • Functional differences between two Tie2 ligands, angiopoietin-1 and -2, in regulation of adult bone marrow hematopoietic stem cells Reviewed

    Yumiko Gomei, Yuka Nakamura, Hiroki Yoshihara, Kentaro Hosokawa, Hiroko Iwasaki, Toshio Suda, Fumio Arai

    Experimental Hematology   38 ( 2 )   2010.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.exphem.2009.11.007

  • Niche Regulation of Hematopoietic Stem Cells in the Endosteum

    Fumio Arai, Hiroki Yoshihara, Kentaro Hosokawa, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Toshio Suda

    Annals of the New York Academy of Sciences   1176 ( 1 )   36 - 46   2009.9

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1749-6632.2009.04561.x

  • Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion

    15 ( 6 )   696 - 700   2009.6

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm.1973

  • Angiopoietins contribute to lung development by regulating pulmonary vascular network formation Reviewed

    Tai Hato, Yoshishige Kimura, Tohru Morisada, Gou Young Koh, Keishi Miyata, Mitsuhisa Tabata, Tsuyoshi Kadomatsu, Motoyoshi Endo, Takashi Urano, Fumio Arai, Kimi Araki, Toshio Suda, Koichi Kobayashi, Yuichi Oike

    Biochemical and Biophysical Research Communications   381 ( 2 )   218 - 223   2009.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2009.02.030

  • Niche regulation of hematopoietic stem cells in the endosteum The role of thrombopoietinmpl signaling in the maintenance of quiescent Hematopoietic Stem Cells

    Fumio Arai, Hiroki Yoshihara, Kentaro Hosokawa, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Toshio Suda

    Hematopoietic Stem Cells VII   36 - 46   2009.1

     More details

    Language:English   Publishing type:Research paper (other academic)  

    DOI: 10.1111/j.1749-6632.2009.04561.x

  • Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice Reviewed

    Haruko Shima, Keiyo Takubo, Hiroko Iwasaki, Hiroki Yoshihara, Yumiko Gomei, Kentaro Hosokawa, Fumio Arai, Takao Takahashi, Toshio Suda

    Biochemical and Biophysical Research Communications   378 ( 3 )   467 - 472   2009.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2008.11.056

  • Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity Reviewed

    Masako Ohmura, Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Haruhiko Shugo, Akira Tamase, Noriyuki Uema, Takako Ooshio, Fumio Arai, Keiyo Takubo, Go Nagamatsu, Isao Hamaguchi, Minoru Takagi, Masahiko Ishihara, Kazuhiro Sakurada, Hiromasa Miyaji, Toshio Suda, Atsushi Hirao

    STEM CELLS   26 ( 12 )   3237 - 3246   2008.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1634/stemcells.2008-0506

  • Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL Reviewed

    Sahoko Matsuoka, Yuichi Oike, Ichiro Onoyama, Atsushi Iwama, Fumio Arai, Keiyo Takubo, Yoichi Mashimo, Hideyuki Oguro, Eriko Nitta, Keisuke Ito, Kana Miyamoto, Hiroki Yoshiwara, Kentaro Hosokawa, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Yasuhide Hayashi, Yumi Matsuzaki, Keiko Nakayama, Yasuo Ikeda, Akira Hata, Shigeru Chiba, Keiichi I. Nakayama, Toshio Suda

    Genes and Development   22 ( 8 )   986 - 991   2008.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1101/gad.1621808

  • Wnt Signaling in the Niche Reviewed

    Toshio Suda, Fumio Arai

    Cell   132 ( 5 )   729 - 730   2008.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.cell.2008.02.017

  • Stem Cell Defects in ATM-Deficient Undifferentiated Spermatogonia through DNA Damage-Induced Cell-Cycle Arrest Reviewed

    Keiyo Takubo, Masako Ohmura, Masaki Azuma, Go Nagamatsu, Wakako Yamada, Fumio Arai, Atsushi Hirao, Toshio Suda

    Cell stem cell   2 ( 2 )   170 - 182   2008.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2007.10.023

  • Function of oxidative stress in the regulation of hematopoietic stem cell-niche interaction Reviewed

    Kentaro Hosokawa, Fumio Arai, Hiroki Yoshihara, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Kana Miyamoto, Haruko Shima, Keisuke Ito, Toshio Suda

    Biochemical and Biophysical Research Communications   363 ( 3 )   578 - 583   2007.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2007.09.014

  • Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche

    Fumio Arai, Toshio Suda

    Hematopoietic Stem Cells VI   41 - 53   2007.6

     More details

    Language:English   Publishing type:Research paper (other academic)  

    DOI: 10.1196/annals.1392.005

  • Foxo3a Is Essential for Maintenance of the Hematopoietic Stem Cell Pool Reviewed

    Kana Miyamoto, Kiyomi Y. Araki, Kazuhito Naka, Fumio Arai, Keiyo Takubo, Satoshi Yamazaki, Sahoko Matsuoka, Takeshi Miyamoto, Keisuke Ito, Masako Ohmura, Chen Chen, Kentaro Hosokawa, Hiromitsu Nakauchi, Keiko Nakayama, Keiichi I. Nakayama, Mine Harada, Noboru Motoyama, Toshio Suda, Atsushi Hirao

    Cell stem cell   1 ( 1 )   101 - 112   2007.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2007.02.001

  • Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice Reviewed

    M. Ninomiya, A. Abe, A. Katsumi, J. Xu, M. Ito, F. Arai, T. Suda, M. Ito, H. Kiyoi, T. Kinoshita, T. Naoe

    Leukemia   21 ( 1 )   136 - 142   2007.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/sj.leu.2404432

  • 精子形成におけるNucleosteminの役割

    大村 昌子, 仲 一仁, 吉田 松生, 新井 文用, 木下 雅史, 玉瀬 玲, 田久保 圭誉, 澤田 元, 須田 年生, 平尾 敦

    解剖学雑誌   82 ( Suppl. )   249 - 249   2007.3

     More details

    Language:Japanese  

  • Role of Stem Cell Niche in the Maintenance of Hematopoietic Stem Cells

    Arai Fumio, Suda Toshio

    27 ( 2 )   117 - 123   2007.3

     More details

    Language:English  

    Role of Stem Cell Niche in the Maintenance of Hematopoietic Stem Cells
    The quiescent state in the cell cycle is thought to be indispensable for the maintenance of hematopoietic stem cells (HSCs). The interaction between HSCs and their niche is critical for maintaining the stem cell properties of HSCs, including self-renewal capacity and the ability of differentiation into single or multiple lineages. The niche cells produce signaling molecules, extracellular matrix, and cell adhesion molecules, and regulate stem cell fates. HSCs balance quiescence and cell division in the stem cell niche for long-term sustaining of hematopoiesis in the niche. Recently, long-term repopulating (LT)-HSCs exist frequently in endosteal surface of trabecular bone area in bone marrow (BM), and it was clarified that an osteoblastic cells function as a niche cells for HSCs. The specific properties of HSC are dynamically controlled by the signalings of receptor/ligand and cell adhesion molecules produced by osteoblastic cells. We have recently reported that side-population (SP) cells in HSCs are in the quiescent state of cell cycle. Cell adhesion of HSCs to the osteoblastic niche enhanced the ability of HSCs to become quiescent, resulting in protection of the HSC compartment from stresses suppressing hematopoiesis.

    DOI: 10.2492/inflammregen.27.117

  • Regulation of reactive oxygen species by Atm is essential for proper response to DNA double-strand breaks in lymphocytes Reviewed

    Keisuke Ito, Keiyo Takubo, Fumio Arai, Hitoshi Satoh, Sahoko Matsuoka, Masako Ohmura, Kazuhito Naka, Masaki Azuma, Kana Miyamoto, Kentaro Hosokawa, Yasuo Ikeda, Tak W. Mak, Toshio Suda, Atsushi Hirao

    Journal of Immunology   178 ( 1 )   103 - 110   2007.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.4049/jimmunol.178.1.103

  • Premeiotic germ cell defect in seminiferous tubules of Atm-null testis Reviewed

    Keiyo Takubo, Atsushi Hirao, Masako Ohmura, Masaki Azuma, Fumio Arai, Go Nagamatsu, Toshio Suda

    Biochemical and Biophysical Research Communications   351 ( 4 )   993 - 998   2006.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2006.10.145

  • 組織幹細胞マーキング法の開発

    大村 昌子, 仲 一仁, 新井 文用, 木下 雅史, 玉瀬 玲, 松岡 佐保子, 伊藤 圭介, 宮本 佳奈, 田久保 圭誉, 須田 年生, 平尾 敦

    臨床血液   47 ( 9 )   1036 - 1036   2006.9

     More details

    Language:Japanese  

  • 造血ニッチによる幹細胞制御 Reviewed

    新井文用

    臨床血液   47 ( 5 )   2006.5

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

  • Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells Reviewed

    Keisuke Ito, Atsushi Hirao, Fumio Arai, Keiyo Takubo, Sahoko Matsuoka, Kana Miyamoto, Masako Ohmura, Kazuhito Naka, Kentaro Hosokawa, Yasuo Ikeda, Toshio Suda

    Nature medicine   12 ( 4 )   446 - 451   2006.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nm1388

  • Regulation of Hematopoietic Stem Cells and Interactions with Stem Cell Niche

    ARAI Fumio

    Journal of oral biosciences   48 ( 1 )   22 - 29   2006.2

     More details

    Language:English  

    Regulation of Hematopoietic Stem Cells and Interactions with Stem Cell Niche
    Long-term bone marrow (BM) repopulating (LTR)-hematopoietic stem cells (HSCs) exist frequently in BM trabecular bone surfaces, and it was clarified that osteoblasts (OBs) are critical for sustaining HSCs. The interaction of HSCs with their particular microenvironments, known as stem cell niches, is critical for maintaining their stem cell properties, including self-renewal capacity and the ability to differentiate into single or multiple lineages. In the niche, the fates of HSCs are regulated by the signaling molecules, extracellular matrix, and cell adhesion molecules produced by osteoblasts. Interaction of HSCs with their stem cell niches is critical for cell cycle regulation of HSCs. Especially, the quiescence of the cell cycle is thought to be an indispensable property for the maintenance of HSCs. We demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and anti-apoptotic, transplantable and comprise a side-population (SP) of HSCs, which contact closely with angiopoietin-1 (Ang-1), a ligand for Tie2, expressing osteoblasts in the BM niche. The interaction of Tie2 and Ang-1 regulates the functional criteria of HSCs in the BM niche, including quiescence, anti-apoptosis and cell adhesion.

    DOI: 10.2330/joralbiosci.48.22

  • Regulation of Hematopoiesis and Its Interaction with Stem Cell Niches

    Fumio Arai, Atsushi Hirao, Toshio Suda

    International Journal of Hematology   82 ( 5 )   371 - 376   2005.12

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1532/ijh97.05100

  • Regulation of stem cells in the niche Reviewed

    Toshio Suda, Fumio Arai, Shigeto Shimmura

    Cornea   24 ( 8 SUPPL. )   S12 - S17   2005.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  • Hematopoietic stem cells and their niche Reviewed

    Toshio Suda, Fumio Arai, Atsushi Hirao

    Trends in Immunology   26 ( 8 )   426 - 433   2005.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.it.2005.06.006

  • Regulation of hematopoiesis by the osteoblastic niche Reviewed

    Arai, F.

    Clinical calcium   15 ( 7 )   2005.8

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

  • Regulation of self-renewal of hematopoietic stem cells in the niche Reviewed

    Hirao, A., Arai, F., Ito, K., Suda, T.

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   50 ( 7 )   2005.6

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

  • Regulation of hematopoietic stem cells by the niche Reviewed

    Fumio Arai, Atsushi Hirao, Toshio Suda

    Trends in Cardiovascular Medicine   15 ( 2 )   75 - 79   2005.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.tcm.2005.03.002

  • Regulation of cell cycle in hematopoietic stem cells by the niche Reviewed

    Atsushi Hirao, Fumio Arai, Toshio Suda

    Cell Cycle   3 ( 12 )   1481 - 1483   2004.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.4161/cc.3.12.1281

  • Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells Reviewed

    Keisuke Ito, Atsushi Hirao, Fumio Arai, Sahoko Matsuoka, Keiyo Takubo, Isao Hamaguchi, Kana Nomiyama, Kentaro Hosokawa, Kazuhiro Sakurada, Naomi Nakagata, Yasuo Ikeda, Tak W. Mak, Toshio Suda

    Nature   431 ( 7011 )   997 - 1002   2004.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nature02989

  • Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration

    Y. Oike, K. Yasunaga, Y. Ito, S.-i. Matsumoto, H. Maekawa, T. Morisada, F. Arai, N. Nakagata, M. Takeya, Y. Masuho, T. Suda

    Proceedings of the National Academy of Sciences   100 ( 16 )   9494 - 9499   2003.8

     More details

    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.1531901100

  • Mast cell-released novel angiopoietin-related growth factor (AGF) promotes angiogenesis and epidermal proliferation Reviewed

    Y Oike, Y Ito, K Yasunaga, S Matsumoto, H Maekawa, F Arai, K Hamada, K Miyata, Y Masuho, T Suda

    CIRCULATION   106 ( 19 )   276 - 277   2002.11

     More details

    Language:English  

  • Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells Reviewed

    Yuichi Oike, Yasuhiro Ito, Koichi Hamada, Xiu Qin Zhang, Keishi Miyata, Fumio Arai, Tomohisa Inada, Kimi Araki, Naomi Nakagata, Motohiro Takeya, Yaz Y. Kisanuki, Masashi Yanagisawa, Nicholas W. Gale, Toshio Suda

    Blood   100 ( 4 )   1326 - 1333   2002.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood.v100.4.1326.h81602001326_1326_1333

  • Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation Reviewed

    Fumio Arai, Osamu Ohneda, Takeshi Miyamoto, Xiu Qin Zhang, Toshio Suda

    Journal of Experimental Medicine   195 ( 12 )   1549 - 1563   2002.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1084/jem.20011700

  • ALCAM (CD166) Its role in hematopoietic and endothelial development Reviewed

    Osamu Ohneda, Kinuko Ohneda, Fumio Arai, James Lee, Takeshi Miyamoto, Yoshimi Fukushima, Donald Dowbenko, Laurence A. Lasky, Toshio Suda

    Blood   98 ( 7 )   2134 - 2142   2001.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood.V98.7.2134

  • Bifurcation of osteoclasts and dendritic cells from common progenitors Reviewed

    Takeshi Miyamoto, Osamu Ohneda, Fumio Arai, Katsuya Iwamoto, Seiji Okada, Katsumasa Takagi, Dirk M. Anderson, Toshio Suda

    Blood   98 ( 8 )   2544 - 2554   2001.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood.V98.8.2544

  • An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor KB ligand Reviewed

    Takeshi Miyamoto, Fumio Arai, Osamu Ohneda, Katsumasa Takagi, Dirk M. Anderson, Toshio Suda

    Blood   96 ( 13 )   4335 - 4343   2000.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1182/blood.v96.13.4335.h8004335_4335_4343

  • WECHE: A novel hematopoietic regulatory factor Reviewed

    Osamu Ohneda, Kinuko Ohneda, Hisayuki Nomiyama, Zhong Zheng, Steven A. Gold, Fumio Arai, Takeshi Miyamoto, Bruce E. Taillon, Richard A. McIndoe, Richard A. Shimkets, David A. Lewin, Toshio Suda, Laurence A. Lasky

    Immunity   12 ( 2 )   141 - 150   2000.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/s1074-7613(00)80167-3

  • WECHE A novel hematopoietic regulatory factor Reviewed

    Osamu Ohneda, Kinuko Ohneda, Hisayuki Nomiyama, Zhong Zheng, Steven A. Gold, Fumio Arai, Takeshi Miyamoto, Bruce E. Taillon, Richard A. McIndoe, Richard A. Shimkets, David A. Lewin, Toshio Suda, Laurence A. Lasky

    Journal of Cultural Heritage   1 ( 2 )   141 - 150   2000.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  • Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor κB (RANK) receptors Reviewed

    190 ( 12 )   1741 - 1754   1999.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor κB (RANK), and have demonstrated that BANK expression in early-stage of precursor cells (c- Fms+RANK-) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms+RANK+) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK-RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.

    DOI: 10.1084/jem.190.12.1741

  • Macrophage-stimulating protein (MSP) and its receptor, RON, stimulate human osteoclast activity but not proliferation: Effect of MSP distinct from that of hepatocyte growth factor Reviewed

    N. Kurihara, J. Tatsumi, F. Arai, A. Iwama, T. Suda

    Experimental Hematology   26 ( 11 )   1080 - 1085   1998.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  • 23(S)25(R)-1,25-Dihydroxyvitamin D_3-lactone, a naturally occurring metabolite of1,25-dihydroxyvitamin D_3, inhibits osteoclast-like cell formation in human bone marrow cultures Reviewed

    KURIHARA Noriyoshi, ISHIZUKA Seiichi, TATSUMI Junichi, ARAI Fumio, IKEDA Katsumi, ROODMAN G. David

    Journal of bone and mineral metabolism   16 ( 1 )   5 - 10   1998.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    23(S)25(R)-1,25-dihydroxyvitamin D-3-lactone, a naturally occurring metabolite of 1,25-dihydroxyvitamin D-3, inhibits osteoclast-like cell formation in human bone marrow cultures

    DOI: 10.1007/s007740050021

  • The N-terminal fragment of osteocalcin is released during osteoclastic bone resorption in vitro Reviewed

    KURIHARA Noriyoshi, HOSODA Kenji, TATSUMI Junichi, YAMAJI Teizo, HOSHIHARA Eiyoshi, ARAI Fumio, IKEDA Katsumi

    Journal of bone and mineral metabolism   16 ( 1 )   11 - 16   1998.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The N-terminal fragment of osteocalcin is released during osteoclastic bone resorption in vitro

    DOI: 10.1007/s007740050022

▼display all

Presentations

  • Function of Pot1 in the maintenance of hematopoietic stem cell activity under stress Invited International conference

    Fumio Arai

    5th International Conference on Tissue Engineering & Regenerative Medicine  2016.9 

     More details

    Event date: 2016.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Germany  

  • Pot1 maintains hematopoietic stem cell activity under stress Invited International conference

    Fumio Arai

    Japan Society for the Promotion of Science and National University of Singapore joint symposium  2016.1 

     More details

    Event date: 2016.1

    Language:English   Presentation type:Oral presentation (general)  

    Country:Singapore  

  • Introduction of hematopoietic stem cell niche Invited International conference

    Fumio Arai

    ISEH 44th Annual Scientific Meeting  2015.9 

     More details

    Event date: 2015.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  • Pot1a regulates self-renewal activity of hematopoietic stem cells Invited International conference

    Fumio Arai

    4th International Conference on Tissue Engineering & Regenerative Medicine  2015.7 

     More details

    Event date: 2015.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Italy  

  • Role of Pot1 in the regulation of hematopoietic stem cell activity Invited International conference

    Fumio Arai

    2015 US-Japan Meeting on Malignant Hematopoiesis and Stem Cells  2015.3 

     More details

    Event date: 2015.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  • Regulation of hematopoietic stem cells in the niche Invited International conference

    Arai, Fumio

    Hematopoietic Stem Cells VII.  2011.9 

     More details

    Event date: 2011.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Germany  

  • Maintenance of stem cells in the niche Invited International conference

    Arai, Fumio

    International Conference and Workshop. Hematopoietic Stem Cells VI.  2006.9 

     More details

    Event date: 2006.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Germany  

  • Regulation of hematopoietic stem cell and its interaction with stem cell niche. Invited International conference

    Arai, Fumio

    Hiroshima conference on education and science in dentistry  2006.1 

     More details

    Event date: 2006.1

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  • Hematopoietic stem cells and their niche. Invited International conference

    Arai, Fumio, Ito, Keisuke, Suda, Toshio

    The International Society on Thrombosis & Haemostasis 20th Congress. 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:Australia  

  • Regulation of hematopoietic stem cells in the osteoblastic niche Invited International conference

    Arai, Fumio

    1st International Conference on Osteoimmunology: Interaction of the Immune and Skeletal Systems. 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:Greece  

  • Regulation of the hematopoietic stem cell and its interaction with the osteoblastic niche Invited International conference

    Arai, Fumio

    Gordon Research Conference, Bone & Teeth 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  • Niche regulation of hematopoietic stem cells in the endosteum Invited International conference

    Arai, Fumio

    International Conference and Workshop. Hematopoietic Stem Cells VII. 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:Germany  

  • Hematopoietic Stem Cell Niche in Bone Marrow Invited

    Arai, Fumio

    2nd Annual Congress of Regenerative Medicine & Stem Cell at CMBF 2009 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:China  

  • Hematopoietic Stem Cells in the Niche Invited International conference

    Arai, Fumio

    2009 World Stem Cell Summit 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  • Regulation of Hematopoietic Stem Cells in the Niche Invited International conference

    Arai, Fumio

    International Society of Inflammation and Regeneration  2011.6 

     More details

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  • 幹細胞のニッチ制御 Invited

    新井文用

    第7回日本再生医療学会総会 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:名古屋   Country:Japan  

  • Hematopoietic stem cells and their niche. Invited International conference

    Arai, Fumio, Ito, Keisuke, Suda, Toshio

    The International Society on Thrombosis & Haemostasis 20th Congress. 

     More details

    Language:English  

    Venue:Sydney   Country:Australia  

    researchmap

  • 幹細胞のニッチ制御 Invited

    新井文用

    第7回日本再生医療学会総会 

     More details

    Language:Japanese  

    Venue:名古屋   Country:Japan  

    researchmap

  • Regulation of the hematopoietic stem cell and its interaction with the osteoblastic niche Invited International conference

    Arai, Fumio

    Gordon Research Conference, Bone & Teeth 

     More details

    Language:English  

    Venue:University of New England, Biddeford, ME   Country:United States  

    researchmap

  • Regulation of hematopoietic stem cells in the osteoblastic niche Invited International conference

    Arai, Fumio

    1st International Conference on Osteoimmunology: Interaction of the Immune and Skeletal Systems. 

     More details

    Language:English  

    Venue:Crete   Country:Greece  

    researchmap

  • Niche regulation of hematopoietic stem cells in the endosteum Invited International conference

    Arai, Fumio

    International Conference and Workshop. Hematopoietic Stem Cells VII. 

     More details

    Language:English  

    Venue:Meersburg   Country:Germany  

    researchmap

  • Hematopoietic Stem Cells in the Niche Invited International conference

    Arai, Fumio

    2009 World Stem Cell Summit 

     More details

    Language:English  

    Venue:Baltimore, MD   Country:United States  

    researchmap

  • 間葉系幹細胞におけるテロメア保護因子Pot1aは、B細胞分化に重要である(POT1a is essential for mesenchymal niches supporting B cell development)

    Nakashima Kentaro, Kunisaki Yuya, Hosokawa Kentaro, Yao Hisayuki, Yuta Ryosuke, Akashi Koichi, Ohga Shouichi, Arai Fumio

    日本小児血液・がん学会雑誌  2022.10  (一社)日本小児血液・がん学会

     More details

    Language:English  

  • 白血病幹細胞の維持と白血病細胞の増殖における骨髄ニッチの役割(The role of the bone marrow niche in leukemic stem cell maintenance and leukemic cell progression)

    Nguyen Ngan, Yao Hisayuki, Hosokawa Kentaro, Yuta Ryosuke, Esaki Yuki, Arai Fumio

    日本血液学会学術集会  2023.10  (一社)日本血液学会

     More details

    Language:English  

▼display all

MISC

  • Niche regulation of hematopoietic stem cells in the endosteum Invited Reviewed

    Fumio Arai, Hiroki Yoshihara, Hosokawa Kentaro, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Toshio Suda

    Ann N Y Acad Sci   1176   36 - 46   2009.10   ISSN:1749-6632

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    During postnatal life, the bone marrow (BM) supports both the self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized niches. The interaction of HSCs with their niches also regulates the quiescence of HSCs. HSC quiescence is critical to ensure lifelong hematopoiesis and to protect the HSC pool from myelotoxic insult and premature exhaustion under conditions of hematopoietic stress. Here we identified long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, Mp1, as a quiescent population in adult BM. THPO was produced by bone-lining cells in the endosteum. Inhibition and stimulation of the THPO/Mp1 pathway produced opposite effects on the quiescence of LT-HSC. Exogenous THPO transiently increased the quiescent LT-HSC population, such as side-population and pyronin Y-negative cells. In contrast, administration of an anti-Mp1 neutralizing antibody, AMM2, suppressed the quiescence of LT-HSCs and enabled HSC engraftment without irradiation, indicating that inhibition of THPO/Mp1 signaling reduces HSC-niche interactions. Moreover, it suggests that inhibiting the HSC-niche interaction could represent a novel technique for bone marrow transplantation without irradiation. Altogether, these data suggest that the THPO/Mp1 signaling pathway is a novel niche component in the endosteum, and in the steady-state condition, this signaling pathway plays a critical role in the regulation of LT-HSCs in the osteoblastic niche.

    DOI: 10.1111/j.1749-6632.2009.04561.x

  • 【老化と血液細胞】Pot1a導入による造血幹細胞の老化制御と機能回復

    新井 文用

    血液内科   87 ( 3 )   290 - 295   2023.9   ISSN:2185-582X

     More details

    Language:Japanese   Publisher:(有)科学評論社  

  • 造血幹細胞の老化制御に対するテロメア結合因子Pot1aの機能解析

    細川 健太郎, Ben D MACARTHUR, 生島 芳子, 外山 弘文, 舛廣 善和, 花澤 重正, 須田 年生, 新井 文用

    臨床血液   2017.9

     More details

    Language:Japanese  

    <p>繰り返し起こる細胞分裂や老化に伴ってDNA損傷が蓄積し幹細胞機能が低下するが,その分子機構には不明な点が多い。今回我々はshelterin複合体の構成因子の一つ,Pot1aの造血幹細胞における発現は,テロメアDNAの損傷応答の抑制や,老化に伴って低下する幹細胞活性を維持するのに重要であることを明らかにした。まず我々は,Pot1aは造血幹細胞において高発現し,老化と共に低下することを見出した。またPot1aを発現抑制すると,テロメアDNAの損傷応答が増加し,造血幹細胞が老化の表現型を呈し,長期骨髄再構成能も著しく低下することが分かった。一方で,外因性Pot1aタンパク質処理を行うことによって,テロメアDNAの損傷応答を抑制し,造血幹細胞活性の低下を抑えることができた。また,老化した造血幹細胞においても幹細胞活性を一部回復させる効果があった。今回の知見は,老化による幹細胞の活性低下を抑制する技術の開発,および医療応用の基盤となることが期待される。</p>

    DOI: 10.11406/rinketsu.58.942

  • 白血病幹細胞とニッチ (特集 白血病発症の分子生物学)

    新井 文用

    血液内科 = Hematology   2016.12

     More details

    Language:Japanese  

  • 幹細胞研究における一細胞解析 (AYUMI 一細胞遺伝子解析)

    新井 文用

    医学のあゆみ   2016.7

     More details

    Language:Japanese  

  • PROTECTION OF TELOMERES 1 (POT1) REGULATES HEMATOPOIETIC STEM CELL ACTIVITY DURING AGEING

    Kentaro Hosokawa, Ben D. MacArthur, Shigemasa Hanazawa, Toshio Suda, Fumio Arai

    EXPERIMENTAL HEMATOLOGY   2015.9

     More details

    Language:English  

  • 造血ニッチ分子研究の現状と展望

    新井 文用

    血液内科   2015.2

     More details

    Language:Japanese  

  • POT1 REGULATES SELF-RENEWAL ACTIVITY OF CORD BLOOD HEMATOPOIETIC STEM CELLS

    Kentaro Hosokawa, Yoshiko Ikushima, Benjamin MacArthur, Toshio Suda, Fumio Arai

    EXPERIMENTAL HEMATOLOGY   2014.8

     More details

    Language:English  

  • 造血幹細胞・白血病幹細胞とニッチ制御 (第1土曜特集 癌幹細胞) -- (造血系癌幹細胞)

    新井 文用

    医学のあゆみ   2014.7

     More details

    Language:Japanese  

  • トップランナーに聞く : 最先端の医療に挑む若手研究者への直撃インタビュー(40)細胞の対称・非対称分裂制御による造血幹細胞の増幅

    新井 文用

    最新医学   2014.4

     More details

    Language:Japanese  

  • SHELTERIN COMPONENT PROTECTION OF TELOMERES 1 (POT1) PLAYS A CRITICAL ROLE IN THE SELF-RENEWAL OF HSCS

    Kentaro Hosokawa, Toshio Suda, Fumio Arai

    EXPERIMENTAL HEMATOLOGY   2013.8

     More details

    Language:English  

  • A PML-PPAR-delta Pathway for Fatty Acid Oxidation Regulates Hematopoietic Stem Cell Maintenance Through the Control of Asymmetric Division.

    Keisuke Ito, Arkaitz Carracedo, Fumio Arai, Ugo Ala, David Avigan, Zachary Schafer, Ron M. Evans, Toshio Suda, Chih-Hao Lee, Pier Paolo Pandolfi

    BLOOD   2012.11

     More details

    Language:English  

  • FUNCTIONAL ANALYSIS OF POT1 IN THE MAINTENANCE OF HEMATOPOIETIC STEM CELLS

    Kentaro Hosokawa, Fumio Arai, Yumiko Nojima, Toshio Suda

    EXPERIMENTAL HEMATOLOGY   2012.8

     More details

    Language:English  

  • Prostaglandin E2 Signaling Through the EP4 Receptor Regulates the Proliferation of Hematopoietic Stem/Progenitor Cells Under Stress Conditions

    Fumio Arai, Yoshiko Matsumoto, Toshio Suda

    BLOOD   2011.11

     More details

    Language:English  

  • Role of Protection of Telomeres 1A (Pot1a) In the Regulation of Hematopoietic Stem Cells

    Fumio Arai, Kentaro Hosokawa, Yumiko Nojima, Toshio Suda

    BLOOD   2010.11

     More details

    Language:English  

  • 境界領域 知っておきたい 造血幹細胞ニッチと骨芽細胞

    新井 文用

    臨床整形外科   2010.5

     More details

    Language:Japanese  

  • 造血幹細胞とニッチ制御 : 最近の展開

    新井 文用

    血液・腫瘍科   2010.3

     More details

    Language:Japanese  

  • Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells (vol 12, pg 446, 2006)

    Keisuke Ito, Atsushi Hirao, Fumio Arai, Keiyo Takubo, Sahoko Matsuoka, Kana Miyamoto, Masako Ohmura, Kazuhito Naka, Kentaro Hosokawa, Yasuo Ikeda, Toshio Suda

    NATURE MEDICINE   2010.1

     More details

    Language:English  

    DOI: 10.1038/nm0110-129a

  • Fractionated Osteoblastic Niche Cells Enhances the Homing Activity of Hematopoietic Stem Cells

    Fumio Arai, Yuka Nakamura, Kentaro Hosokawa, Isao Kobayashi, Hiroko Iwasaki, Yumiko Gomei, Hiroki Yoshihara, Toshio Suda

    BLOOD   2009.11

     More details

    Language:English  

  • トロンボポエチントランスジェニックマウスモデルを用いた骨髄線維症の発症機構の解析

    咸 明姫, 久保田 義顕, 田久保 圭誉, 鄒 鵬, 中村 由香, 吉原 宏樹, 細川 健太郎, 五明 由美子, 新井 文用, 須田 年生

    臨床血液   2009.9

     More details

    Language:Japanese  

  • 幹細胞ニッチ (第5土曜特集 細胞医療Update) -- (幹細胞の基礎研究)

    新井 文用

    医学のあゆみ   2009.5

     More details

    Language:Japanese  

  • 幹細胞ニッチにおけるWntシグナルの意義

    新井 文用

    血液・腫瘍科   2008.12

     More details

    Language:Japanese  

  • Functional Difference of Two Tie2 Ligands, Angiopoietin-1 and-2, in the Regulation of the Adult Bone Marrow Hematopoietic Stem Cells

    Yumiko Gomei, Fumio Arai, Hiroki Yoshihara, Hiroko Iwasaki, Kentaro Hosokawa, Yuka Nakamura, Toshio Suda

    BLOOD   2008.11

     More details

    Language:English  

  • Control of the HSC Niche Signaling for the Efficient Long-Term Engraftment of Hematopoietic Stem Cells without Irradiation or High-Dose Chemotherapy.

    Hiroki Yoshihara, Fumio Arai, Kentaro Hosokawa, Takao Takahashi, Hiroshi Miyazaki, Toshio Suda

    BLOOD   2008.11

     More details

    Language:English  

  • 造血幹細胞の内骨膜ニッチ (特集 ベールを脱ぐニッチ--見えてきた幹細胞の居場所)

    新井 文用

    細胞工学   2008.7

     More details

    Language:Japanese  

  • Role of cyclin-dependent kinase inhibitor p57(kip2) in the regulation of hematopoietic stem cell quiescence

    Hiroki Yoshihara, Peng Zou, Fumio Arai, Kentaro Hosokawa, Keiyo Takubo, Takao Takahashi, Toshio Suda

    EXPERIMENTAL HEMATOLOGY   2008.7

     More details

    Language:English  

  • 幹細胞のニッチ制御とがん幹細胞 (特集 がん幹細胞研究の進展)

    新井 文用

    血液・腫瘍科   2008.6

     More details

    Language:Japanese  

  • 造血幹細胞のニッチ制御 (特集 造血細胞におけるシグナル伝達)

    新井 文用

    細胞   2007.11

     More details

    Language:Japanese  

  • Expression of endothelial protein C receptor confines hematopoietic stem cell in murine fetal liver

    Hiroko Iwasaki, Fumio Arai, Yoshiaki Kubota, Toshio Suda

    BLOOD   2007.11

     More details

    Language:English  

  • HIF-1αを介した骨髄低酸素環境における造血幹細胞の静止期維持

    田久保 圭誉, 平尾 敦, 合田 亘人, 新井 文用, 細川 健太郎, 吉原 宏樹, Johnson Randall, 末松 誠, 須田 年生

    臨床血液   2007.9

     More details

    Language:Japanese  

  • 造血幹細胞と骨芽細胞ニッチ (あゆみ 幹細胞とニッチ)

    新井 文用, 須田 年生

    医学のあゆみ   2007.5

     More details

    Language:Japanese  

  • 造血幹細胞とニッチ

    新井 文用, 須田 年生

    生体の科学   2007.5

     More details

    Language:Japanese  

  • Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche Reviewed

    Fumio Arai, Toshio Suda

    Annals of the New York Academy of Sciences   2007.4

     More details

    Language:English  

    DOI: 10.1196/annals.1392.005

  • Ubiquitin ligase component fbw7 regulates the quiescence of hematopoietic stem cells.

    Sahoko Matsuoka, Yuichi Oike, Ichiro Onoyama, Keiyo Takubo, Keisuke Ito, Fumio Arai, Yasuo Ikeda, Keiko Nakayama, Keiichi Nakayama, Toshio Suda

    BLOOD   2006.11

     More details

    Language:English  

  • Anti-oxidant NAC prevents hypersensitivity, immunodeficiency and lymphomagenesis in Atm(-/-) mice.

    Keisuke Ito, Fumio Arai, Sahoko Matsuoka, Yasuo Ikeda, Toshio Suda, Atsushi Hirao

    BLOOD   2006.11

     More details

    Language:English  

  • Foxo3a is essential for the quiescence and self-renewal of hematopoietic stem cells.

    Kana Miyamoto, Atsushi Hirao, Kiyomi Y. Araki, Fumio Arai, Kazuhito Naka, Keiyo Takubo, Sahoko Matsuoka, Satoshi Yamazaki, Keisuke Ito, Masako Ohmura, Kentaro Hosokawa, Mine Harada, Noboru Motoyama, Toshio Suda

    BLOOD   2006.11

     More details

    Language:English  

  • Reactive oxygen species control hematopoietic stem cell-niche interaction through the regulation of N-cadherin.

    Kentaro Hosokawa, Fumio Arai, Hiroki Yoshihara, Keiyo Takubo, Keisuke Ito, Sahoko Matsuoka, Toshio Suda

    BLOOD   2006.11

     More details

    Language:English  

  • Thrombopoietin-MpI signal induces hematopoietic stem cells into quiescent state in the bone marrow niche.

    Hiroki Yoshihara, Fumio Arai, Kentaro Hosokawa, Takao Takahashi, Hiroshi Miyazaki, Toshio Suda

    BLOOD   2006.11

     More details

    Language:English  

  • 骨髄低酸素ニッチにおけるHIF-1αを介した静止期造血幹細胞の制御機構

    田久保 圭誉, 平尾 敦, 合田 亘人, 新井 文用, Randall Johnson, 末松 誠, 須田 年生

    臨床血液   2006.9

     More details

    Language:Japanese  

  • ユビキチンリガーゼコンポーネントFbw7は造血幹細胞の静止状態を制御する

    松岡 佐保子, 尾池 雄一, 小野山 一郎, 田久保 圭誉, 伊藤 圭介, 新井 文用, 岩間 厚志, 池田 康夫, 中山 啓子, 中山 敬一, 須田 年生

    臨床血液   2006.9

     More details

    Language:Japanese  

  • 活性酸素種(ROS)の接着制御による造血幹細胞のニッチからの離脱機構の解析

    細川 健太郎, 新井 文用, 伊藤 圭介, 田久保 圭誉, 吉原 宏樹, 松岡 佐保子, 須田 年生

    臨床血液   2006.9

     More details

    Language:Japanese  

  • 転写因子FOXO3a欠損による造血幹細胞の自己複製能の低下

    宮本 佳奈, 平尾 敦, 新井 文用, 松岡 佐保子, 伊藤 圭介, 田久保 圭誉, 仲 一仁, 大村 昌子, 細川 健太郎, 原田 実根, 本山 昇, 須田 年生

    臨床血液   2006.9

     More details

    Language:Japanese  

  • Rb plays an essential role in erythroid differentiation through inhibition of apoptosis mediated by NFKB.

    S Matsuoka, A Hirao, F Arai, K Takubo, K Miyamoto, K Hosokawa, T Suda

    BLOOD   2005.11

     More details

    Language:English  

  • Inactivation of p38 MAPK extends self-renewal capacity of haematopoietic stem

    K Ito, A Hirao, F Arai, S Matsuoka, K Takubo, Y Ikeda, T Suda

    BLOOD   2005.11

     More details

    Language:English  

  • Special Review ニッチにある造血幹細胞とその細胞周期制御

    須田 年生, 新井 文用

    細胞工学   2005.10

     More details

    Language:Japanese  

  • 酸化ストレスによるp38MAPKを介した造血幹細胞枯渇誘導

    伊藤 圭介, 田久保 圭誉, 新井 文用, 松岡 佐保子, 須田 年生, 平尾 敦

    日本血液学会・日本臨床血液学会総会プログラム・抄録集   2005.9

     More details

    Language:Japanese  

  • 造血幹細胞のニッチと自己複製制御機構

    平尾 敦, 新井 文用, 伊藤 圭介

    蛋白質核酸酵素   2005.6

     More details

    Language:Japanese  

  • 2等賞 ニッチにおける静止期造血幹細胞の制御 (ベルツ賞 2004年度受賞論文抄録紹介)

    須田 年生, 新井 文用, 平尾 敦

    日本医師会雑誌   2005.3

     More details

    Language:Japanese  

  • 特報 第41回ベルツ賞受賞論文:ニッチにおける静止期造血幹細胞の制御

    須田 年生, 新井 文用, 平尾 敦

    最新医学   2005.2

     More details

    Language:Japanese  

  • 造血幹細胞の微小環境「ニッチ」

    新井 文用, 平尾 敦, 須田 年生

    生物物理化学 = Journal of Electrophoresis   2004.12

     More details

    Language:Japanese  

  • Role of cell adhesion in the maintenance of hematopoietic stem cells in the bone marrow niche.

    F Arai, A Hirao, K Hosokawa, T Suda

    BLOOD   2004.11

     More details

    Language:English  

  • Identification of non-hematopoietic stem cells in mouse bone marrow osteoblastic zone.

    H Sato, F Arai, M Shibata, A Hirao, T Suda, K Sakurada

    BLOOD   2004.11

     More details

    Language:English  

  • Rb regulates erythroid differentiation through Bcl-XL-dependent anti-apoptotic effect.

    S Matsuoka, A Hirao, F Arai, K Ito, K Takubo, K Nomiyama, Hamaguchi, I, Y Ikeda, T Suda

    BLOOD   2004.11

     More details

    Language:English  

  • Regulation of oxidative stress by ATM is required for the self-renewal of haematopoietic stem cells

    K Ito, A Hirao, F Arai, S Matsuoka, TW Mak, T Suda

    BLOOD   2004.11

     More details

    Language:English  

  • 幹細胞とそのニッチ(微小環境)について

    須田 年生, 宮本 健史, 新井 文用, 平尾 敦

    日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association   2004.9

     More details

    Language:Japanese  

  • ATM(Ataxia telangiectasia mutated)の造血幹細胞の再構築能における役割 レドックスと自己複製

    伊藤 圭介, 平尾 敦, 新井 文用, 松岡 佐保子, 田久保 圭誉, 須田 年生

    日本血液学会・日本臨床血液学会総会プログラム・抄録集   2004.9

     More details

    Language:Japanese  

  • Rb欠損にみられる赤血球分化異常は,Bcl-XLによって回復する

    松岡 佐保子, 平尾 敦, 新井 文用, 濱口 功, 伊藤 圭介, 田久保 圭誉, 野見山 佳奈, 池田 康夫, 須田 年生

    日本血液学会・日本臨床血液学会総会プログラム・抄録集   2004.9

     More details

    Language:Japanese  

  • Tie2/angiopoietin-1 regulates quiescence of hematopoietic stem cells in a niche.

    A Hirao, F Arai, T Suda

    BLOOD   2003.11

     More details

    Language:English  

  • Identification of quiescent hematopoietic stem cells in side population

    A Hirao, F Arai, T Suda

    EXPERIMENTAL HEMATOLOGY   2003.7

     More details

    Language:English  

  • Ang1/Tie2 signaling regulates quiescence of hematopoietic stem cell in niche

    F Arai, A Hirao, T Suda

    EXPERIMENTAL HEMATOLOGY   2003.7

     More details

    Language:English  

  • Role of EphB4 in the vasculogenesis in bone development

    XQ Zhang, N Takakura, F Arai, T Miyamoto, H Sokamoto, T Suda

    BLOOD   2001.11

     More details

    Language:English  

  • Ephrin-Eph signaling between endothelial cells and surrounding mesenchymal cells plays an essential role in vasculo-angiogenesis

    Y Oike, XQ Zhang, Y Ito, K Hamada, K Miyata, F Arai, S Suenobu, N Takakura, T Suda

    CIRCULATION   2000.10

     More details

    Language:English  

▼display all

Professional Memberships

  • The Japanese Society of Hematology

  • American Society of Hematology

  • International Society for Stem Cell Research

  • International Society for Experimental Hematology

  • Stem Cell Research Symposium

  • European Hematology Association

  • The Japanese Society of Hematology

      More details

  • Stem Cell Research Symposium

      More details

  • International Society for Stem Cell Research

      More details

  • International Society for Experimental Hematology

      More details

  • American Society of Hematology

      More details

▼display all

Committee Memberships

  • Councilor   Domestic

    2019.10 - 2021.9   

  • Organizer   Domestic

    2017.5 - Present   

  • 幹細胞シンポジウム   幹事  

    2017.5   

      More details

Academic Activities

  • Screening of academic papers

    Role(s): Peer review

    2024

     More details

    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:1

  • Screening of academic papers

    Role(s): Peer review

    2021

     More details

    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:1

  • その他

    第16回幹細胞シンポジウム  ( 九州大学医学部百年講堂 Japan ) 2018.6

     More details

    Type:Competition, symposium, etc. 

    Number of participants:130

  • その他

    第76回日本血液学会学術集会  ( 大阪国際会議場 Japan ) 2014.10 - 2014.11

     More details

    Type:Competition, symposium, etc. 

  • その他

    第12回幹細胞シンポジウム  ( 福岡県福岡市、九州大学医学部百年講堂 Japan ) 2014.5

     More details

    Type:Competition, symposium, etc. 

    Number of participants:500

Research Projects

  • Function of telomere binding factors in normal and tumor hematopoietic microenvironments

    Grant number:23K07861  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

      More details

    Grant type:Scientific research funding

    CiNii Research

  • Elucidation of the mechanism of hematopoietic stem cell maintenance by newly identified bone marrow mesenchymal stem cells.

    Grant number:23K27626  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

      More details

    Grant type:Scientific research funding

    CiNii Research

  • 新たに同定した骨髄間葉系幹細胞による造血幹細胞の維持機構の解明

    Grant number:23H02935  2023 - 2025

    日本学術振興会  科学研究費助成事業  基盤研究(B)

      More details

    Authorship:Principal investigator  Grant type:Scientific research funding

  • Overcoming T cell dysfunction with Shelterin factor

    Grant number:23K18301  2023 - 2024

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Challenging Research(Exploratory)

      More details

    Authorship:Principal investigator  Grant type:Scientific research funding

    CiNii Research

  • Identification of transcriptional signaling networks that control the quality and quantity of the bone marrow microenvironment

    Grant number:20K08733  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hosokawa Kentaro

      More details

    Grant type:Scientific research funding

    In this study, we aimed to clarify the function of the forkhead transcription factor Foxp2 on hematopoietic support and self-renewal in bone marrow mesenchymal stem cells (MSCs), and analyzed MSC-specific Foxp2-deficient mice. We found that MSCs exhibit decreased self-renewal capacity and decreased expression of hematopoietic supporting factors. Furthermore, we found that the effects of Foxp2 deficiency on the cell cycle and metabolism of hematopoietic stem cells (HSCs) resulted in a decrease in self-renewal capacity and bone marrow remodeling capacity.

    CiNii Research

  • シェルタリン因子による造血微小環境(ニッチ)の機能制御メカニズムの解明

    Grant number:20H03711  2020 - 2023

    日本学術振興会  科学研究費助成事業  基盤研究(B)

      More details

    Authorship:Principal investigator  Grant type:Scientific research funding

  • シェルタリン因子による造血微小環境(ニッチ)の機能制御メカニズムの解明

    Grant number:20H03711  2020 - 2022

    日本学術振興会  科学研究費助成事業  基盤研究(B)

      More details

    Grant type:Scientific research funding

  • 老化ニッチによる造血幹細胞の分裂制御異常の分子機構

    2020

    上原記念生命科学財団研究助成金

      More details

    Authorship:Principal investigator  Grant type:Contract research

  • シェルタリン因子を用いた造血幹細胞の機能再生と増幅系の確立

    2019 - 2021

    再生医療実現拠点ネットワークプログラム技術開発個別課題

      More details

    Authorship:Principal investigator  Grant type:Contract research

  • 白血病幹細胞におけるシェルタリン因子TIN2の機能解明と新規治療法開発への応用

    Grant number:19K22638  2019 - 2020

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

      More details

    Grant type:Scientific research funding

  • 次世代型人工ニッチを用いた造血幹細胞の非対称分裂制御機構の解明と体外増幅

    Grant number:17H04208  2017 - 2019

    日本学術振興会  科学研究費助成事業  基盤研究(B)

      More details

    Grant type:Scientific research funding

  • 造血幹細胞の未分化性維持に対する転写因子Foxp2の機能解析

    Grant number:17K09907  2017 - 2019

    日本学術振興会  科学研究費助成事業  基盤研究(C)

      More details

    Grant type:Scientific research funding

  • 幹細胞の非対称分裂を規定する微小環境(ニッチ)シグナル経路の解明

    2017 - 2018

    武田科学振興財団生命科学研究助成

      More details

    Authorship:Principal investigator  Grant type:Contract research

  • 造血幹細胞の非対称分裂機構の解明 International coauthorship

    2014.4

    九州大学大学院医学研究院(日本) 

      More details

    Authorship:Principal investigator 

  • テロメアDNA損傷回避による造血幹細胞の老化抑制と体外増幅

    Grant number:26293228  2014 - 2016

    日本学術振興会  科学研究費助成事業  基盤研究(B)

      More details

    Grant type:Scientific research funding

  • 造血幹細胞の対称性分裂制御子の機能解析と細胞分裂操作への応用

    Grant number:26670471  2014 - 2015

    科学研究費助成事業  挑戦的萌芽研究

      More details

    Grant type:Scientific research funding

  • 細胞分裂制御(対称・非対称分裂)の操作による造血幹細胞増幅

    2010 - 2013

    最先端・次世代研究開発支援プログラム

      More details

    Authorship:Principal investigator  Grant type:Contract research

  • 人工幹細胞ニッチ:造血ニッチ複合体の再構成による幹細胞増幅

    Grant number:21679004  2009 - 2010

    科学研究費助成事業  若手研究(S)

      More details

    Grant type:Scientific research funding

  • 造血幹細胞-骨芽細胞ニッチ相互作用の成立・維持の分子機構

    Grant number:18689024  2006 - 2008

    科学研究費助成事業  若手研究(A)

      More details

    Grant type:Scientific research funding

  • 造血幹細胞ニッチと細胞分裂制御

    Grant number:16002011  2004 - 2008

    日本学術振興会  科学研究費助成事業  特別推進研究

      More details

    Grant type:Scientific research funding

  • 造血幹細胞の支持細胞「ニッチ細胞」としての骨芽細胞の機能解析

    Grant number:16790542  2004 - 2005

    科学研究費助成事業  若手研究(B)

      More details

    Grant type:Scientific research funding

  • M-CSF,RANKLによる破骨細胞の分化誘導と機能発現に関する研究

    Grant number:00J04597  2000 - 2002

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

      More details

    Grant type:Scientific research funding

  • M-CSF,RANKLによる破骨細胞の分化誘導と機能発現に関する研究

    2000 - 2002

    日本学術振興会  特別研究員

      More details

    Grant type:Joint research

▼display all

Class subject

  • 生命の科学A

    2021.4 - 2021.9   First semester

  • 基礎生物学講義

    2020.4 - 2020.9   First semester

  • 応用幹細胞学講義

    2020.4 - 2020.9   First semester

  • 応用幹細胞学

    2019.10 - 2020.3   Second semester

  • 生命の科学A

    2019.6 - 2019.8   Summer quarter

  • 分子生物学概論

    2019.4 - 2019.9   First semester

  • 生命の科学A

    2019.4 - 2019.6   Spring quarter

  • 生命の科学A

    2018.4 - 2018.6   Spring quarter

▼display all

FD Participation

  • 2024.3   Role:Panelist   Title:九州大学医学部・医学系学府合同教育FD

    Organizer:[Undergraduate school/graduate school/graduate faculty]

  • 2017.12   Title:大学院FD

  • 2017.6   Title:医学科・生命科学科FD

  • 2016.12   Title:大学院FD

  • 2016.10   Title:馬出地区キャンパスFD

  • 2015.12   Role:Participation   Title:大学院FD

    Organizer:[Undergraduate school/graduate school/graduate faculty]

  • 2015.8   Role:Participation   Title:医学科・生命科学科FD

    Organizer:Undergraduate school department

  • 2014.8   Role:Participation   Title:医学科・生命科学科FD

    Organizer:[Undergraduate school/graduate school/graduate faculty]

▼display all

Acceptance of Foreign Researchers, etc.

  • Acceptance period: 2020.6 - 2021.3  

    Nationality:Viet Nam